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        "titulo" => "El montelukast&#44; un inhibidor de leucotrienos&#44; reduce la inflamaci&#243;n pulmonar aguda inducida por LPS y la activaci&#243;n de neutr&#243;filos humanos"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acute respiratory distress syndrome &#40;ARDS&#41; is characterized by hypoxemic respiratory failure associated with acute pulmonary inflammation and edema presenting high mortality rates&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> Different etiologies&#44; such as head&#44; chest and other major injuries&#44; as well as sepsis&#44; inhalation of harmful substances and severe pneumonia may result in the development of ARDS&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#8211;3</span></a> Although the mechanisms underlying the pathophysiology of ARDS are not completely understood&#44; in all cases&#59; especially in bacterial infections&#44; an exacerbated inflammatory response plays a central role&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">While several animal models have been established to study ARDS&#44; lipopolysaccharide &#40;LPS&#41; is the most widely used as it reproduces several important ARDS features&#44; such as the accrual of neutrophils in alveolar and in interstitial space and in bronchoalveolar lavage &#40;BAL&#41;&#44; the accumulation of proteinaceous debris in alveolar spaces&#44; thickening of the alveolar wall&#44; and increased concentration of total proteins and pro-inflammatory cytokines in BAL&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">2&#8211;5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">LPS signals via toll like receptor 4 &#40;TLR4&#41; and activates nuclear factor kappa B &#40;NF-&#954;B&#41;&#44; a key regulator of the inflammatory process&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">3&#8211;6</span></a> NF-&#954;B is a transcription factor regulating several aspects of ARDS pathophysiology&#44; such as production of pro-inflammatory cytokines &#40;i&#46;e&#46; IL-1beta&#44; IL-6&#44; IL-8&#47;CXCL-1 and TNF-&#945;&#41;&#44; and also the lung fibroproliferative response in murine models of ARDS&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">7&#8211;10</span></a> NF-&#954;B also regulates human and mouse fibroblast differentiation&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">11</span></a> a key event that occurs during fibroproliferation&#44; an important process following lung injury&#46; Therefore&#44; pharmacological approaches that inhibit NF-&#954;B expression and activation may attenuate lung inflammatory and fibrotic responses following injury&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">3&#8211;5&#44;10&#8211;12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Cys leukotrienes receptor-1 &#40;cysLTR1&#41; antagonists montelukast&#44; pranlukast and zafirlukast are small molecules that have demonstrated secondary&#44; off-target&#44; anti-inflammatory effects including the inhibition of cyclic nucleotides phosphodiesterases and 5&#8242;-lypoxygenase as well as NF-&#954;B downregulation&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Taken together&#44; this study tested the hypothesis that montelukast inhibits both acute lung injury induced by LPS in mice and LPS-induced human neutrophil activation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Montelukast Reduces Leukocyte Number in Bronchoalveolar Lavage &#40;BAL&#41;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Similarly to the leukocyte response during ARDS&#44; oral-tracheal administration of LPS results in a significant increase in the number of lung leukocytes&#46; At 24<span class="elsevierStyleHsp" style=""></span>h&#44; BAL leukocytes were significantly increased in mice injured with LPS &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; To mimic an ARDS therapeutic scenario&#44; mice received oral-tracheal administration of montelukast 24<span class="elsevierStyleHsp" style=""></span>h post-LPS injury and were sacrificed 24<span class="elsevierStyleHsp" style=""></span>h later&#46; At 48<span class="elsevierStyleHsp" style=""></span>h&#44; total number of BAL cells remained significantly increased&#44; however&#44; montelukast significantly reduced the number of cells in the BAL &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46; At 24<span class="elsevierStyleHsp" style=""></span>h post-LPS treatment&#44; differential cell counts of BAL fluid revealed a significant increase in the number of macrophages&#44; neutrophils and lymphocytes compared to PBS treated controls &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#44; E&#44; G&#41;&#46; Montelukast treatment at 24<span class="elsevierStyleHsp" style=""></span>h&#44; significantly attenuated the accumulation of macrophages &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#44; neutrophils &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>F&#41;&#44; and lymphocytes at 48<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>H&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Montelukast Reduces Vascular Permeability and Cytokines in Bronchoalveolar Lavage &#40;BAL&#41;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Compared to PBS treated mice&#44; increased vascular permeability was evident by increased protein concentration in BAL fluid at 24<span class="elsevierStyleHsp" style=""></span>h post-LPS treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41; and remained at 48<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#44; while Montelukast treatment at 24<span class="elsevierStyleHsp" style=""></span>h post-LPS reduced the total amount of BAL proteins &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; At 24<span class="elsevierStyleHsp" style=""></span>h post-LPS treatment&#44; ELISA detected increased levels of proinflammatory cytokines IL-6 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C&#41;&#44; CXCL1&#47;KC &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>E&#41;&#44; TNF-&#945; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>G&#41; and IL-17 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>I&#41;&#46; At 48<span class="elsevierStyleHsp" style=""></span>h post-LPS treatment&#44; cytokines remained high&#58; IL-6 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>D&#41;&#44; CXCL1&#47;KC &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>F&#41;&#44; TNF-&#945; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>H&#41; and IL-17 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>J&#41;&#44; but were effectively reduced by therapeutic administration of Montelukast&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Montelukast Reduces Neutrophils&#44; Lymphocytes and Macrophages Accumulation in the Lung Parenchyma</span><p id="par0040" class="elsevierStylePara elsevierViewall">Indeed&#44; at 24 and 48<span class="elsevierStyleHsp" style=""></span>h post-LPS treatment&#44; morphometric analysis revealed increased numbers of parenchymal neutrophils &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#44; B&#41;&#44; lymphocytes &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>C&#44; D&#41;&#44; and macrophages &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>E&#44; F&#41;&#46; Treatment with Montelukast significantly reduced the number of immune cells in the lung parenchyma &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>B&#44; D&#44; F&#41;&#46; Representative images of PBS &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>G&#41;&#44; LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>I&#41;&#44; LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>48<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>H&#41;&#44; and 96 LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Montelukast &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>J&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Montelukast Inhibits NF-&#954;B and Leukotriene B4 Receptor &#40;LTB4R&#41; Expression in the Lung Parenchyma</span><p id="par0045" class="elsevierStylePara elsevierViewall">In the present study&#44; increased expression of NF-&#954;B by parenchymal leukocytes for both periods studied &#40;24<span class="elsevierStyleHsp" style=""></span>h and 48<span class="elsevierStyleHsp" style=""></span>h&#41; post-LPS stimulation compared with PBS groups &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>A and B&#41; was observed&#46; The results also revealed that Montelukast efficiently reduced the NF-&#954;B expression &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B&#41;&#46; LTB4 signals mainly via LTB4R&#44; which results in the recruitment of neutrophils&#46; The present study demonstrated that LPS stimulation at 24<span class="elsevierStyleHsp" style=""></span>h and 48<span class="elsevierStyleHsp" style=""></span>h resulted in increased expression of LTB4R by parenchymal leukocytes &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>C and D&#41; while Montelukast significantly reduced the LTB4R expression &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>D&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>E&#8211;H shows representative photomicrographs of NF-kB for PBS48<span class="elsevierStyleHsp" style=""></span>h&#44; LPS24<span class="elsevierStyleHsp" style=""></span>h&#44; LPS48<span class="elsevierStyleHsp" style=""></span>h and LPS48h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>montelukast groups&#44; respectively&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Montelukast Restores VEGF Expression in LPS-injured Lungs</span><p id="par0050" class="elsevierStylePara elsevierViewall">Treatment with LPS decreased VEGF expression at 24<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>A&#41; and furthermore at 48<span class="elsevierStyleHsp" style=""></span>h while Montelukast administration at 24<span class="elsevierStyleHsp" style=""></span>h resulted in a recovery of VEGF expression in BAL compared to control &#40;PBS&#41; treated animals &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>B&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Montelukast Reduces IL-8 Release by Human Neutrophils</span><p id="par0055" class="elsevierStylePara elsevierViewall">Human neutrophils were stimulated with LPS &#40;1&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mL&#41; for 1<span class="elsevierStyleHsp" style=""></span>h and then incubated with Montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M in PBS&#41; for an additional 5<span class="elsevierStyleHsp" style=""></span>h&#46; ELISA for IL-8 was performed on the supernatant&#46; Montelukast treatment significantly inhibited LPS-stimulated production of IL-8 &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>A&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">The present study demonstrates for the first time that leukotriene inhibitor Montelukast reduces both acute LPS-induced lung inflammation in mice as well as LPS-induced human neutrophils activation&#46; Exacerbated inflammation plays a central role in the pathogenesis of ARDS&#59; therefore in the quest to develop effective ARDS therapies&#44; reducing inflammation has been a main goal&#46; The off-target effects of Montelukast on LTB4 receptors present on neutrophils could have beneficial implications in ARDS therapy&#46; Leukotriene B4 &#40;LTB4&#41; is synthesized primarily by activated basophils&#44; eosinophils&#44; monocytes and macrophages and acts in both an autocrine and paracrine manner by signaling to structural cells&#44; neutrophils and TH2 lymphocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">14</span></a> Though neutrophils express a low level of LTB4 receptor&#44; LTB4 acts as a strong chemoattractant of neutrophils&#44; a cell centrally involved in ARDS&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">While the recognition of the involvement of leukotriene pathways in asthma prompted the development of leukotriene receptor inhibitors&#44; drugs such as Montelukast&#44; a leukotriene inhibitor&#44; have not yet been tested in the context of ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">15</span></a> Twenty-five years ago&#44; a swine LPS model of acute lung injury &#40;ALI&#41; demonstrated that the LTBR1 competitive receptor antagonist LY255283 reduced ALI&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">16</span></a> However&#44; unlike Montelukast&#44; this agent did not exhibit potent off target anti-inflammatory effects such as the inhibition of cyclooxygenase or 5-lipoxygenase enzymes&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a> Therefore&#44; in the case of ARDS&#44; Montelukast may be an effective inhibitor of inflammation not only because of its ability to inhibit leukotriene signaling&#44; but also via off-target effects which result in a net increase in cyclic adenosine monophosphate &#40;cAMP&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> and the suppression of NF-kB<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> which leads to the attenuation of cytokine production and a dispersal of lung immune cells&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">This study used the LPS-induced acute lung injury model in mice to test the hypothesis that the Montelukast would attenuate lung inflammation&#46; Our results indicated that Montelukast reduced the LPS-induced increase in total immune cells both in the BAL&#44; suggesting decreased vascular permeability&#44; and in the lung parenchyma&#46; In addition&#44; Montelukast treated mice displayed significantly reduced levels of cytokines IL-6&#44; CXCL1&#47;KC&#44; IL-17 and TNF-&#945; suggesting attenuation of inflammatory processes due to LPS&#46; LPS-induced pulmonary dysfunction was associated with increased neutrophil count&#44; leukotriene &#40;LT&#41; B4&#44; and tumor necrosis factor &#40;TNF&#41;-&#945; in BALF&#46; These results suggest that treatment with Montelukast can be useful in chronic airway inflammatory diseases including COPD poorly responsive to glucocorticoids&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">20</span></a> In addition&#44; Montelukast treated mice also displayed reduced LTB4R and NF-&#954;B expression in the lung parenchyma&#44; which correlates to decreased leukotriene signaling and decreased inflammation and Montelukast was able to block LTD&#40;4&#41;-induced stimulation&#46; Allergen challenge leads to a significant increase in sCD14 concentrations in BAL and might modulate the allergen-induced inflammation&#46; In addition&#44; LTD&#40;4&#41; might play a role in the release of sCD14&#44; and it could be speculated that sCD14 reduction by LTRA might contribute to the mechanisms of LTRA in the treatment of allergic asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">21</span></a> Moreover&#44; LTB&#40;4&#41;- and LTD&#40;4&#41;-induced eosinophil activation was attenuated by CP-105&#44;696 and the Cys-LT&#40;1&#41; receptor antagonist montelukast&#44; respectively&#44; highlighting specific receptor dependency&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a> Thus&#44; mediator-triggered granulocyte activation and antiapoptotic pathways are distinct events that can be differentially regulated&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">22</span></a> Lastly&#44; our results presented herein indicates that Montelukast treatment resulted in a recovery of VEGF expression in the BAL&#44; a measurement which is associated with recovery in ARDS patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">23&#8211;25</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">While neutrophils themselves do not produce LTB4&#44; and LTB4 receptors are expressed only at low levels&#44; exposure to LTB4 primes neutrophils to produce copious amounts of reactive oxygen species &#40;ROS&#41;&#44; matrix metalloproteinases &#40;MMPs&#41; and other cytokines upon stimulation by additional cytokines&#46; Human neutrophils activated with the chemoattractant N-formyl-<span class="elsevierStyleSmallCaps">l</span>-methionyl-<span class="elsevierStyleSmallCaps">l</span>-leucyl-<span class="elsevierStyleSmallCaps">l</span>-phenylalanine &#40;fMLP&#41; in combination with cytochalasin B resulted in abrupt and sustained increases in cytosolic Ca<span class="elsevierStyleSup">2</span>&#40;&#43;&#41;&#44; as well as release of elastase and production of superoxide and LTB4&#44; and expression of macrophage complement receptor 3 &#40;CR3&#41;&#46; These effects were attenuated with Montelukast treatment and the literature point out its association with significant increases in cyclic AMP&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> In this study&#44; human neutrophils were stimulated with LPS which signals via TLR4 and activates NF-kB-signaling resulting in the production of cytokines&#44; particularly IL-8&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a> Stimulation with LPS for 1<span class="elsevierStyleHsp" style=""></span>h&#44; followed by one treatment of Montelukast resulted in a significant reduction of IL-8 in the cell supernatant&#46; Given the low level of LTBR4 receptor expression by neutrophils&#44; this study also suggests that an important off-target effect of Montelukast is the ability to attenuate NF-kB signaling&#44; likely through upstream mechanisms that increase intracellular cAMP&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">An interesting point that should be highlighted is the fact that our results showed herein a reduction of circulating levels of IL-17 in Montelukast-treated mice with acute lung inflammation&#46; Therefore&#44; from our results&#44; is possible suggest that the Th17 cells could be a bystander mediator of Montelukast effect in vivo&#44; since that IL-17 is produced by Th17 cells&#44; and this subset expresses high levels of LTB4R1 and CysTLR1&#44; being attracted by leukotrienes &#40;especially LTD4&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In conclusion&#44; this is the first study to report the effects of Montelukast in an LPS mouse model of ARDS and in LPS-stimulated human neutrophils activation&#46; These results concur not only the potent anti-inflammatory nature of Montelukast but also its ability to signal via LTB4R independent pathways&#46; Future studies should further explore the nature of these mechanisms especially in the context of human neutrophils&#44; a central inflammation mediator of ARDS&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Material and methods</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Experimental Design of Animal Experiments</span><p id="par0090" class="elsevierStylePara elsevierViewall">This study was approved by the ethical committee of Nove de Julho University &#40;AN0002&#47;2015&#41; and were carried out in accordance to Guide for the Care and Use of Laboratory Animals&#44; published by the U&#46;S&#46; National Institutes of Health &#40;NIH publication no&#46; 85-23&#44; revised 1996&#41;&#46; Thirty-eight C57Bl&#47;6 male mice weighing between 20 and 25<span class="elsevierStyleHsp" style=""></span>g were distributed in Control 24<span class="elsevierStyleHsp" style=""></span>h &#40;PBS24<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;&#44; LPS 24<span class="elsevierStyleHsp" style=""></span>h &#40;LPS24<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;&#44; Control 48<span class="elsevierStyleHsp" style=""></span>h &#40;PBS48<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#44; LPS 48<span class="elsevierStyleHsp" style=""></span>h &#40;LPS48<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41; and LPS 48<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>montelukast &#40;LPS 48<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>MK&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#46; For Montelukast administration&#44; animals were anesthetized by intra-peritoneal injection of ketamine &#40;100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; and xylazine &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#46; The PBS24<span class="elsevierStyleHsp" style=""></span>h and LPS24<span class="elsevierStyleHsp" style=""></span>h groups were euthanized 24<span class="elsevierStyleHsp" style=""></span>h after vehicle &#40;PBS 50<span class="elsevierStyleHsp" style=""></span>&#956;l&#41; or LPS &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mouse&#47;50<span class="elsevierStyleHsp" style=""></span>&#956;l PBS&#41; administration&#46; The PBS48<span class="elsevierStyleHsp" style=""></span>h&#44; LPS48<span class="elsevierStyleHsp" style=""></span>h and LPS 48<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>MK groups were euthanized 48<span class="elsevierStyleHsp" style=""></span>h after vehicle &#40;PBS&#59; 50<span class="elsevierStyleHsp" style=""></span>&#956;l&#41; or LPS &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mouse&#47;50<span class="elsevierStyleHsp" style=""></span>&#956;l PBS&#41; administration&#46; Montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M&#47;mouse&#47;50<span class="elsevierStyleHsp" style=""></span>&#956;l PBS&#41; was orotracheally administered 24<span class="elsevierStyleHsp" style=""></span>h after LPS administration and animals were euthanized 24<span class="elsevierStyleHsp" style=""></span>h later&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Assessment of Lung Inflammation</span><p id="par0095" class="elsevierStylePara elsevierViewall">Lung inflammation was assessed through the collection and analysis of bronchoalveolar lavage &#40;BAL&#41;&#46; Quantitative analysis of parenchymal inflammation was performed using histomorphometrical technique&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;31</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The numbers of total and differential cells in BAL were evaluated in the material recovered from 3 gentle washes of 0&#46;5<span class="elsevierStyleHsp" style=""></span>mL of sterile PBS&#44; by using a Neubauer chamber &#40;total cells&#41; and cytospin preparations &#40;differential cell count&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;31</span></a> The cytospins were stained with Diff Quick &#40;Medion Diagnostics&#44; D&#252;dingen&#44; Switzerland&#41;&#44; as previously described&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">27&#8211;32</span></a> In summary&#44; 300<span class="elsevierStyleHsp" style=""></span>cells per slide per mouse were analyzed using an optical microscope and were counted according to the classical hematological criteria&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;34</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The density of neutrophils&#44; lymphocytes and macrophages in the lung parenchyma was evaluated as previously described&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;31</span></a> Briefly&#44; the lungs were excised in block&#44; fixed in 10&#37; formalin solution&#44; at a constant pressure &#40;20<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#41; for 24<span class="elsevierStyleHsp" style=""></span>h&#44; and submitted to histological routine&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Five micrometer lung slices were stained with hematoxylin and eosin and 20 photomicrographs at 400&#215; magnification of each animal of all groups were obtained using an Olympus BX43-L-FL microscope with a camera XM-10&#46; The area of lung tissue in the lung parenchyma was obtained by subtracting the airspace area from the total photo area&#46; Then&#44; the number of neutrophils&#44; lymphocytes and macrophages were counted in each photo according to the morphological criteria&#46; The results were expressed in number of cells&#47;mm2 of lung tissue&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">30&#8211;33</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Total Proteins in BAL</span><p id="par0115" class="elsevierStylePara elsevierViewall">The levels of total proteins in BAL was measured using the BCA Protein Assay Kit &#40;Thermo Scientific&#44; USA&#41; and was used as an index of vascular permeability&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">31</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Cytokines in BAL&#44; Serum and in Cell Culture Supernatants</span><p id="par0120" class="elsevierStylePara elsevierViewall">The levels of IL-6 &#40;Biolegend&#44; Code 431306&#59; Detection limit 7&#46;8<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41;&#44; CXCL1&#47;KC &#40;R&#38;D Systems&#44; Code DY453&#59; Detection limit 15&#46;6<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41;&#44; IL-8 &#40;Biolegend&#44; Code 431506&#59; Detection limit 15&#46;6<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41;&#44; IL-17 &#40;R&#38;D Systems&#44; Code DY421&#59; Detection limit 15&#46;6<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; and TNF-&#945; &#40;Biolegend&#44; Code 430906&#59; Detection limit 7&#46;8<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; in BAL and in cell culture supernatants were measured using ELISA kits from Biolegends &#40;USA&#41; and R&#38;D Systems &#40;USA&#41; as indicated&#44; according to the manufacturers&#8217; recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> The measurements were done in triplicates in all samples&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Immunohistochemical Study</span><p id="par0125" class="elsevierStylePara elsevierViewall">The quantitative analysis of the expression of leukotriene B4 receptor &#40;LTB4R&#41; &#40;sc-98841&#59; Santa Cruz&#44; CA&#44; USA&#41; and of NF-&#954;B p65 &#40;sc-109&#59; Santa Cruz&#44; CA&#44; USA&#41; by parenchymal leukocytes was performed using classical immunohistochemistry protocol&#44; as previously described&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">30&#44;33&#44;34</span></a> Briefly&#44; the area of lung tissue in the lung parenchyma was obtained by subtracting the airspace area from the total photo area&#46; Then&#44; the number of leukocytes positive to LTB4R and NF-kB p65 were counted in each photo&#46; The results were expressed in number of positive cells&#47;mm<span class="elsevierStyleSup">2</span> of lung tissue&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;32</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Isolation and Culture of Human Neutrophils</span><p id="par0130" class="elsevierStylePara elsevierViewall">Eight milliliter of peripheral blood was diluted 1&#58;1 in sterile PBS and added to a tube containing Ficoll Paque gradient and submitted to 20<span class="elsevierStyleHsp" style=""></span>min centrifugation &#40;1200<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">g</span>&#41;&#46; Red cells were lysed&#44; polymorphonuclear cells collected and neutrophils were separated from eosinophils using EasySep&#8482; Human Neutrophil Enrichment Kit &#40;&#35;19257&#59; StemCell Technologies&#44; USA&#41;&#46; The purity was assessed through cytospin analysis and was higher than 98&#37;&#46; Neutrophils &#40;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">6</span>&#47;2<span class="elsevierStyleHsp" style=""></span>mL medium&#47;well&#41; were incubated in 48 well plates in RPMI 1640 medium and were stimulated with LPS &#40;1&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mL medium&#41; for 1<span class="elsevierStyleHsp" style=""></span>h and then incubated with montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M in PBS&#41; for an additional 5<span class="elsevierStyleHsp" style=""></span>h&#46; Supernatant was recovered for measurements of IL-8 by ELISA&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Statistical Analysis</span><p id="par0135" class="elsevierStylePara elsevierViewall">If not stated otherwise&#44; two-way analysis of variance &#40;TWO-WAY ANOVA&#41; followed by Bonferroni post hoc test was used&#46; Significance levels were considered for <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46; Values were expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SEM&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Authorship</span><p id="par0140" class="elsevierStylePara elsevierViewall">JEDC&#44; MCOJ&#44; BM&#44; AD&#44; ARAO&#44; JCJAJ&#44; AAB&#44; NCRO&#44; NRDR&#44; contributed performing the experiments and analysis&#46; APLO&#44; APS&#44; FMCC&#44; FA&#44; HCCFN&#44; and RPV have written the manuscript and critically revised the manuscript and performed the statistical analysis&#46; RPV have designed the study&#46; All authors have reviewed and approved the final version of the manuscript prior to submission&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Some pro-inflammatory lipids derived from 1 lipooxygenase enzyme are potent neutrophil chemoattractant&#44; a cell centrally involved in acute respiratory distress syndrome &#40;ARDS&#41;&#59; a syndrome lacking effective treatment&#46; Considering the beneficial effects of the leukotriene receptor inhibitor&#44; montelukast&#44; on other lung diseases&#44; whether montelukast attenuates inflammation in a mouse model of ARDS&#44; and whether it reduces LPS stimulated activation of human neutrophils was investigated&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Thirty-five C57Bl&#47;6 mice were distributed into control &#40;PBS&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h&#44; LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mouse&#41;&#44; control<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>48<span class="elsevierStyleHsp" style=""></span>h&#44; LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>48<span class="elsevierStyleHsp" style=""></span>h&#44; and LPS 48<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#46; In addition&#44; human neutrophils were incubated with LPS &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mL&#41; and treated with montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Oral-tracheal administration of montelukast significantly attenuated total cells &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; macrophages &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; neutrophils &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#44; lymphocytes &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; and total protein levels in BAL &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; as well as IL-6 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; CXCL1&#47;KC &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; IL-17 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41; and TNF-&#945; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#46; Furthermore&#44; montelukast reduced neutrophils &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; lymphocytes &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; and macrophages &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; in the lung parenchyma&#46; In addition&#44; montelukast restored BAL VEGF levels &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#46; LTB4 receptor expression &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; as well as NF-&#954;B &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; a downstream target of LPS&#44; were also reduced in lung parenchymal leukocytes&#46; Furthermore&#44; montelukast reduced IL-8 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; production by LPS-treated human neutrophils&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In conclusion&#44; montelukast efficiently attenuated both LPS-induced lung inflammation in a mouse model of ARDS and in LPS challenged human neutrophils&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Algunos l&#237;pidos proinflamatorios derivados de la enzima lipooxigenasa 1 son potentes quimioatrayentes de neutr&#243;filos&#44; un tipo celular con una implicaci&#243;n principal en el s&#237;ndrome de distr&#233;s respiratorio agudo &#40;SDRA&#41;&#44; para el que no hay tratamiento efectivo&#46; Considerando los efectos beneficiosos del inhibidor de los receptores de leucotrienos montelukast en otras enfermedades pulmonares&#44; se investig&#243; si este f&#225;rmaco era capaz de atenuar la inflamaci&#243;n en un modelo de rat&#243;n de SDRA y de reducir la activaci&#243;n de los neutr&#243;filos humanos inducida por LPS&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se utilizaron 35 ratones C57BL&#47;6 distribuidos en los siguientes grupos&#58; control &#40;PBS&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h&#44; LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#40;24<span class="elsevierStyleHsp" style=""></span>h &#91;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;rat&#243;n&#93;&#41;&#44; control<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>48<span class="elsevierStyleHsp" style=""></span>h y LPS 48<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#46; Por otro lado&#44; se incubaron neutr&#243;filos humanos con LPS &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; y se trataron con montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La administraci&#243;n orotraqueal de montelukast redujo el n&#250;mero total de c&#233;lulas &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; de macr&#243;fagos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; de neutr&#243;filos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#44; de linfocitos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y los niveles totales de prote&#237;na en el lavado broncoalveolar &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; as&#237; como de IL-6 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; CXCL1&#47;KC &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; IL-17 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; y TNF-&#945; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Adem&#225;s&#44; el montelukast redujo los neutr&#243;filos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; los linfocitos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41; y los macr&#243;fagos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41; en el par&#233;nquima pulmonar&#46; Asimismo&#44; restaur&#243; los niveles de VEGF en el lavado broncoalveolar &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; y disminuy&#243; la expresi&#243;n del receptor LTB4 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y de NF-&#954;B &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; una diana <span class="elsevierStyleItalic">downstream</span> del LPS&#44; en los leucocitos del par&#233;nquima pulmonar&#46; Por &#250;ltimo&#44; redujo la producci&#243;n de IL-8 por parte de los neutr&#243;filos humanos tratados con LPS&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusi&#243;n</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">En conclusi&#243;n&#44; el montelukast atenu&#243; de manera eficaz tanto la inflamaci&#243;n pulmonar inducida por LPS en un modelo de rat&#243;n de SDRA como en neutr&#243;filos humanos estimulados con LPS&#46;</p></span>"
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              "identificador" => "bib0175"
              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute respiratory distress syndrome&#58; the Berlin Definition"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46;M&#46; Ranieri"
                            1 => "G&#46;D&#46; Rubenfeld"
                            2 => "B&#46;T&#46; Thompson"
                            3 => "N&#46;D&#46; Ferguson"
                            4 => "E&#46; Caldwell"
                            5 => "E&#46; Fan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2012.5669"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2012"
                        "volumen" => "307"
                        "paginaInicial" => "2526"
                        "paginaFinal" => "2533"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22797452"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An official American Thoracic Society workshop report&#58; features and measurements of experimental acute lung injury in animals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Matute-Bello"
                            1 => "G&#46; Downey"
                            2 => "B&#46;B&#46; Moore"
                            3 => "S&#46;D&#46; Groshong"
                            4 => "M&#46;A&#46; Matthay"
                            5 => "A&#46;S&#46; Slutsky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/rcmb.2009-0210ST"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2011"
                        "volumen" => "44"
                        "paginaInicial" => "725"
                        "paginaFinal" => "738"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21531958"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Silencing Angiopoietin-Like Protein 4 &#40;ANGPTL4&#41; protects against lipopolysaccharide-induced acute lung injury via regulating SIRT1&#47;NF-kB pathway"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Guo"
                            1 => "S&#46; Li"
                            2 => "Y&#46; Zhao"
                            3 => "P&#46; Qian"
                            4 => "F&#46; Ji"
                            5 => "L&#46; Qian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jcp.24969"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cell Physiol"
                        "fecha" => "2015"
                        "volumen" => "230"
                        "paginaInicial" => "2390"
                        "paginaFinal" => "2402"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25727991"
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                          ]
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                      ]
                    ]
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                ]
              ]
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            3 => array:3 [
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              "etiqueta" => "4"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Magnolol ameliorates lipopolysaccharide-induced acute lung injury in rats through PPAR&#947;-dependent inhibition of NF-kB activation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;H&#46; Lin"
                            1 => "M&#46;C&#46; Chen"
                            2 => "T&#46;H&#46; Chen"
                            3 => "H&#46;Y&#46; Chang"
                            4 => "T&#46;C&#46; Chou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.intimp.2015.05.051"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int Immunopharmacol"
                        "fecha" => "2015"
                        "volumen" => "28"
                        "paginaInicial" => "270"
                        "paginaFinal" => "278"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26072062"
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            4 => array:3 [
              "identificador" => "bib0195"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Asef mediates HGF protective effects against LPS induced lung injury and endothelial barrier dysfunction"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Meng"
                            1 => "A&#46; Meliton"
                            2 => "N&#46; Moldobaeva"
                            3 => "G&#46; Mutlu"
                            4 => "Y&#46; Kawasaki"
                            5 => "T&#46; Akiyama"
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                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1152/ajplung.00170.2014"
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                        "tituloSerie" => "Am J Physiol Lung Cell Mol Physiol"
                        "fecha" => "2015"
                        "volumen" => "308"
                        "paginaInicial" => "L452"
                        "paginaFinal" => "L463"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25539852"
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                      "titulo" => "LPS&#47;TLR4 signal transduction pathway"
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                            0 => "Y&#46;C&#46; Lu"
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                        "tituloSerie" => "Cytokine"
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                        "paginaFinal" => "151"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18304834"
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                    0 => array:2 [
                      "titulo" => "NF-kB binding activity in mixed Bal cells from patients with SIRS and ARDS"
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                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;W&#46; Christman"
                            1 => "A&#46; Venkatakrishnan"
                            2 => "A&#46;P&#46; Wheeler"
                            3 => "G&#46;R&#46; Bernard"
                            4 => "T&#46;S&#46; Blackwell"
                          ]
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                    0 => array:1 [
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                        "tituloSerie" => "Sepsis"
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                        "volumen" => "4"
                        "paginaInicial" => "35"
                        "paginaFinal" => "41"
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "titulo" => "NF-B family 317 of transcription factors&#58; central regulators of innate and adaptive immune functions"
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                          "etal" => false
                          "autores" => array:2 [
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                          ]
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                    0 => array:2 [
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                        "tituloSerie" => "Clin Microbiol Rev"
                        "fecha" => "2002"
                        "volumen" => "15"
                        "paginaInicial" => "414"
                        "paginaFinal" => "429"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12097249"
                            "web" => "Medline"
                          ]
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                ]
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                    0 => array:2 [
                      "titulo" => "The complexity of NF-&#954;B signaling in inflammation and cancer"
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                          "autores" => array:2 [
                            0 => "B&#46; Hoesel"
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Cancer"
                        "fecha" => "2013"
                        "volumen" => "2"
                        "paginaInicial" => "12"
                        "paginaFinal" => "86"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12605718"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0220"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The nuclear factor NF-kappaB pathway in inflammation"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "T&#46; Lawrence"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1101/cshperspect.a001651"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cold Spring Harb Perspect Biol"
                        "fecha" => "2009"
                        "volumen" => "1"
                        "paginaInicial" => "a001651"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20457564"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "11"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nuclear factor &#40;NF&#41;-&#954;B p65 regulates differentiation of human and mouse lung fibroblasts mediated by TGF&#946;"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "X&#46; Sun"
                            1 => "E&#46; Chen"
                            2 => "R&#46; Dong"
                            3 => "W&#46; Chen"
                            4 => "Y&#46; Hu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.lfs.2014.11.033"
                      "Revista" => array:6 [
                        "tituloSerie" => "Life Sci"
                        "fecha" => "2015"
                        "volumen" => "122"
                        "paginaInicial" => "8"
                        "paginaFinal" => "14"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25498897"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0230"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
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                            1 => "F&#46; Zhang"
                            2 => "G&#46; Liu"
                            3 => "R&#46; Wang"
                            4 => "S&#46;D&#46; London"
                            5 => "L&#46; London"
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                        ]
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0057285"
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                        "tituloSerie" => "PLoS ONE"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "e57285"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23437361"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0235"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cysteinyl leukotriene receptor-1 antagonists as modulators of innate immune cell function"
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                          "etal" => false
                          "autores" => array:6 [
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                            1 => "H&#46;C&#46; Steel"
                            2 => "G&#46;R&#46; Tintinger"
                            3 => "C&#46;M&#46; Gravett"
                            4 => "R&#46; Anderson"
                            5 => "C&#46; Feldman"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2014/608930"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Immunol Res"
                        "fecha" => "2014"
                        "volumen" => "2014"
                        "paginaInicial" => "608930"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24971371"
                            "web" => "Medline"
                          ]
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                  ]
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              "identificador" => "bib0240"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction"
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                            4 => "B&#46;G&#46; Monks"
                            5 => "E&#46;A&#46; Kurt-Jones"
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                    0 => array:2 [
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                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2002"
                        "volumen" => "277"
                        "paginaInicial" => "47834"
                        "paginaFinal" => "47843"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12324469"
                            "web" => "Medline"
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                ]
              ]
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              "identificador" => "bib0245"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Pharmacokinetics&#44; bioavailability&#44; 358 and safety of montelukast sodium &#40;MK-0476&#41; in healthy males and females"
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                          "etal" => true
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                            3 => "B&#46;J&#46; Gertz"
                            4 => "M&#46; De Smet"
                            5 => "N&#46; Noonan"
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                      "doi" => "10.1023/a:1016056912698"
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                        "tituloSerie" => "Pharm Res"
                        "fecha" => "1996"
                        "volumen" => "13"
                        "paginaInicial" => "445"
                        "paginaFinal" => "448"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8692739"
                            "web" => "Medline"
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                    ]
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                ]
              ]
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              "identificador" => "bib0250"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "LY255283&#44; a novel leukotriene B4 receptor antagonist&#44; limits activation of neutrophils and prevents acute lung injury induced by endotoxin in pigs"
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                        "paginaInicial" => "191"
                        "paginaFinal" => "198"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8393594"
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                ]
              ]
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              "identificador" => "bib0255"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Pulmonary actions of LY255283&#44; a leukotriene B4 receptor antagonist"
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                  ]
                  "host" => array:1 [
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                        "tituloSerie" => "Eur J Pharmacol"
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                        "paginaInicial" => "57"
                        "paginaFinal" => "64"
                      ]
                    ]
                  ]
                ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Cyclic AMP mediated inhibition of 5-lipoxygenase translocation and leukotriene biosynthesis in human neutrophils"
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                    0 => array:2 [
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12130675"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Inhibition of the NFkappaB transcriptional activity by protein kinase A"
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                        ]
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                    ]
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                        "tituloSerie" => "Eur J Biochem"
                        "fecha" => "2002"
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                        "paginaInicial" => "4559"
                        "paginaFinal" => "4565"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12230568"
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                    0 => array:2 [
                      "titulo" => "Montelukast versus dexamethasone treatment in a guinea pig model of chronic pulmonary neutrophilic inflammation"
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                        "tituloSerie" => "COPD"
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                        "paginaInicial" => "455"
                        "paginaFinal" => "463"
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                          0 => array:2 [
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                          "etal" => false
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                    ]
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                        "paginaFinal" => "311"
                        "link" => array:1 [
                          0 => array:2 [
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                      "titulo" => "Role of leukotrienes in the regulation of human granulocyte behaviour&#58; dissociation between agonist-induced activation and retardation of apoptosis"
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                        "tituloSerie" => "Br J Pharmacol"
                        "fecha" => "2003"
                        "volumen" => "139"
                        "paginaInicial" => "388"
                        "paginaFinal" => "398"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12770944"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0285"
              "etiqueta" => "23"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Vascular endothelial 337 growth factor &#40;VEGF&#41; in acute lung injury &#40;ALI&#41; and acute respiratory distress syndrome &#40;ARDS&#41;&#58; paradox or paradigm&#63;"
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                        0 => array:2 [
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                      ]
                    ]
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                  "host" => array:1 [
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                        "tituloSerie" => "Thorax"
                        "fecha" => "2006"
                        "volumen" => "61"
                        "paginaInicial" => "621"
                        "paginaFinal" => "626"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16807391"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0290"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury"
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                          "etal" => true
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                            1 => "S&#46; Boussat"
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                        "link" => array:1 [
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                      "titulo" => "Interactive inhibitory effects of formoterol and montelukast on activated human neutrophils"
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                            1 => "A&#46;J&#46; Theron"
                            2 => "H&#46;C&#46; Steel"
                            3 => "G&#46;R&#46; Tintinger"
                            4 => "R&#46; Cockeran"
                            5 => "C&#46; Feldman"
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                    0 => array:2 [
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                        "volumen" => "36"
                        "paginaInicial" => "1417"
                        "paginaFinal" => "1424"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20413544"
                            "web" => "Medline"
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                          "autores" => array:6 [
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                            3 => "T&#46; Wada"
                            4 => "N&#46; Mukaida"
                            5 => "K&#46; Matsushima"
                          ]
                        ]
                      ]
                    ]
                  ]
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                        "fecha" => "1994"
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                        "paginaInicial" => "559"
                        "paginaFinal" => "564"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7964163"
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                            "web" => "Medline"
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                0 => array:2 [
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                            1 => "C&#46;R&#46; Olivo"
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                            3 => "A&#46;C&#46; Toledo"
                            4 => "M&#46;A&#46; Martins"
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                        "paginaFinal" => "119"
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                          0 => array:2 [
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                            "web" => "Medline"
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                    0 => array:2 [
                      "titulo" => "Protective effects of aerobic exercise on acute lung injury induced by LPS in mice"
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                            5 => "F&#46;A&#46; dos Santos"
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                    ]
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                        "paginaInicial" => "R199"
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                    ]
                  ]
                ]
              ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low level laser therapy reduces acute lung inflammation in a model of pulmonary and extrapulmonary LPS-induced ARDS"
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                            3 => "R&#46;W&#46; Cust&#243;dio"
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                            5 => "N&#46;R&#46; Damaceno-Rodrigues"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Photochem Photobiol B"
                        "fecha" => "2014"
                        "volumen" => "5"
                        "paginaInicial" => "57"
                        "paginaFinal" => "63"
                      ]
                    ]
                  ]
                ]
              ]
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            31 => array:3 [
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              "etiqueta" => "32"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation"
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                          "etal" => true
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                            0 => "K&#46; Baudi&#223;"
                            1 => "C&#46;K&#46; Ayata"
                            2 => "Z&#46; Lazar"
                            3 => "S&#46; Cicko"
                            4 => "J&#46; Beckert"
                            5 => "A&#46; Meyer"
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                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00080014"
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                        "fecha" => "2015"
                        "volumen" => "45"
                        "paginaInicial" => "1669"
                        "paginaFinal" => "1680"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25614161"
                            "web" => "Medline"
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                      ]
                    ]
                  ]
                ]
              ]
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            32 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Aerobic conditioning and allergic pulmonary inflammation in mice II&#46; Effects on lung vascular and parenchymal inflammation and remodeling"
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                            3 => "A&#46;B&#46; Dos Santos"
                            4 => "T&#46; Mauad"
                            5 => "M&#46;A&#46; Martins"
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                      ]
                    ]
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                    0 => array:2 [
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                        "tituloSerie" => "Am J Physiol Lung Cell Mol Physiol"
                        "fecha" => "2008"
                        "volumen" => "295"
                        "paginaInicial" => "L670"
                        "paginaFinal" => "L679"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18757522"
                            "web" => "Medline"
                          ]
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                    ]
                  ]
                ]
              ]
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              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-inflammatory effects of aerobic exercise in mice exposed to air pollution"
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                            2 => "L&#46;B&#46; Silva"
                            3 => "F&#46;M&#46; Almeida"
                            4 => "N&#46;R&#46; Damaceno-Rodrigues"
                            5 => "E&#46;G&#46; Caldini"
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                      ]
                    ]
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                        "fecha" => "2012"
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                        "paginaInicial" => "1227"
                        "paginaFinal" => "1234"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22297803"
                            "web" => "Medline"
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Original Article
Montelukast, Leukotriene Inhibitor, Reduces LPS-Induced Acute Lung Inflammation and Human Neutrophil Activation
El montelukast, un inhibidor de leucotrienos, reduce la inflamación pulmonar aguda inducida por LPS y la activación de neutrófilos humanos
Jaime Eduardo Davino-Chiovattoa,, Manoel Carneiro Oliveira-Juniorb,, BreAnne MacKenzieb,, Alana Santos-Diasb, Ana Roberta Almeida-Oliveirab, Jefferson Comin Jonco Aquino-Juniorb, Auriléia Aparecida Britoa, Nicole Cristine Rigonato-Oliveiraa, Nilsa Regina Damaceno-Rodriguesc, Ana Paula Ligeiro Oliveiraa, Alessandro Pereira Silvad, Fernanda Marciano Consolim-Colomboa, Flavio Aimbiree, Hugo Caire Castro-Faria-Netof, Rodolfo Paula Vieirab,g,h,i,
Corresponding author
rodrelena@yahoo.com.br

Corresponding author.
a Nove de Julho University (UNINOVE), São Paulo, SP, Brazil
b Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), São José dos Campos, SP, Brazil
c University of São Paulo, School of Medicine, Department of Pathology (LIM 59), São Paulo, SP, Brazil
d Post-graduation Program in Biomedical Engineering, University of Mogi das Cruzes, Mogi das Cruzes, SP, Brazil
e Federal University of Sao Paulo (UNIFESP), São José dos Campos, SP, Brazil
f Laboratory of Immunopharmacology, Osvaldo Cruz Institute (IOC), Osvaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil
g Universidade Brasil, Post-graduation Program in Bioengineering and in Biomedical Engineering, São Paulo, SP, Brazil
h Federal University of Sao Paulo (UNIFESP), Post-graduation Program in Sciences of Human Movement and Rehabilitation, Santos, SP, Brazil
i Anhembi Morumbi University, School of Medicine, Avenida Deputado Benedito Matarazzo 4050, São José dos Campos, SP, Brazil
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acute respiratory distress syndrome &#40;ARDS&#41; is characterized by hypoxemic respiratory failure associated with acute pulmonary inflammation and edema presenting high mortality rates&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> Different etiologies&#44; such as head&#44; chest and other major injuries&#44; as well as sepsis&#44; inhalation of harmful substances and severe pneumonia may result in the development of ARDS&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#8211;3</span></a> Although the mechanisms underlying the pathophysiology of ARDS are not completely understood&#44; in all cases&#59; especially in bacterial infections&#44; an exacerbated inflammatory response plays a central role&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">While several animal models have been established to study ARDS&#44; lipopolysaccharide &#40;LPS&#41; is the most widely used as it reproduces several important ARDS features&#44; such as the accrual of neutrophils in alveolar and in interstitial space and in bronchoalveolar lavage &#40;BAL&#41;&#44; the accumulation of proteinaceous debris in alveolar spaces&#44; thickening of the alveolar wall&#44; and increased concentration of total proteins and pro-inflammatory cytokines in BAL&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">2&#8211;5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">LPS signals via toll like receptor 4 &#40;TLR4&#41; and activates nuclear factor kappa B &#40;NF-&#954;B&#41;&#44; a key regulator of the inflammatory process&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">3&#8211;6</span></a> NF-&#954;B is a transcription factor regulating several aspects of ARDS pathophysiology&#44; such as production of pro-inflammatory cytokines &#40;i&#46;e&#46; IL-1beta&#44; IL-6&#44; IL-8&#47;CXCL-1 and TNF-&#945;&#41;&#44; and also the lung fibroproliferative response in murine models of ARDS&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">7&#8211;10</span></a> NF-&#954;B also regulates human and mouse fibroblast differentiation&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">11</span></a> a key event that occurs during fibroproliferation&#44; an important process following lung injury&#46; Therefore&#44; pharmacological approaches that inhibit NF-&#954;B expression and activation may attenuate lung inflammatory and fibrotic responses following injury&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">3&#8211;5&#44;10&#8211;12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Cys leukotrienes receptor-1 &#40;cysLTR1&#41; antagonists montelukast&#44; pranlukast and zafirlukast are small molecules that have demonstrated secondary&#44; off-target&#44; anti-inflammatory effects including the inhibition of cyclic nucleotides phosphodiesterases and 5&#8242;-lypoxygenase as well as NF-&#954;B downregulation&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Taken together&#44; this study tested the hypothesis that montelukast inhibits both acute lung injury induced by LPS in mice and LPS-induced human neutrophil activation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Montelukast Reduces Leukocyte Number in Bronchoalveolar Lavage &#40;BAL&#41;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Similarly to the leukocyte response during ARDS&#44; oral-tracheal administration of LPS results in a significant increase in the number of lung leukocytes&#46; At 24<span class="elsevierStyleHsp" style=""></span>h&#44; BAL leukocytes were significantly increased in mice injured with LPS &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; To mimic an ARDS therapeutic scenario&#44; mice received oral-tracheal administration of montelukast 24<span class="elsevierStyleHsp" style=""></span>h post-LPS injury and were sacrificed 24<span class="elsevierStyleHsp" style=""></span>h later&#46; At 48<span class="elsevierStyleHsp" style=""></span>h&#44; total number of BAL cells remained significantly increased&#44; however&#44; montelukast significantly reduced the number of cells in the BAL &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46; At 24<span class="elsevierStyleHsp" style=""></span>h post-LPS treatment&#44; differential cell counts of BAL fluid revealed a significant increase in the number of macrophages&#44; neutrophils and lymphocytes compared to PBS treated controls &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#44; E&#44; G&#41;&#46; Montelukast treatment at 24<span class="elsevierStyleHsp" style=""></span>h&#44; significantly attenuated the accumulation of macrophages &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#44; neutrophils &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>F&#41;&#44; and lymphocytes at 48<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>H&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Montelukast Reduces Vascular Permeability and Cytokines in Bronchoalveolar Lavage &#40;BAL&#41;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Compared to PBS treated mice&#44; increased vascular permeability was evident by increased protein concentration in BAL fluid at 24<span class="elsevierStyleHsp" style=""></span>h post-LPS treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41; and remained at 48<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#44; while Montelukast treatment at 24<span class="elsevierStyleHsp" style=""></span>h post-LPS reduced the total amount of BAL proteins &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; At 24<span class="elsevierStyleHsp" style=""></span>h post-LPS treatment&#44; ELISA detected increased levels of proinflammatory cytokines IL-6 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C&#41;&#44; CXCL1&#47;KC &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>E&#41;&#44; TNF-&#945; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>G&#41; and IL-17 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>I&#41;&#46; At 48<span class="elsevierStyleHsp" style=""></span>h post-LPS treatment&#44; cytokines remained high&#58; IL-6 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>D&#41;&#44; CXCL1&#47;KC &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>F&#41;&#44; TNF-&#945; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>H&#41; and IL-17 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>J&#41;&#44; but were effectively reduced by therapeutic administration of Montelukast&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Montelukast Reduces Neutrophils&#44; Lymphocytes and Macrophages Accumulation in the Lung Parenchyma</span><p id="par0040" class="elsevierStylePara elsevierViewall">Indeed&#44; at 24 and 48<span class="elsevierStyleHsp" style=""></span>h post-LPS treatment&#44; morphometric analysis revealed increased numbers of parenchymal neutrophils &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#44; B&#41;&#44; lymphocytes &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>C&#44; D&#41;&#44; and macrophages &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>E&#44; F&#41;&#46; Treatment with Montelukast significantly reduced the number of immune cells in the lung parenchyma &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>B&#44; D&#44; F&#41;&#46; Representative images of PBS &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>G&#41;&#44; LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>I&#41;&#44; LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>48<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>H&#41;&#44; and 96 LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Montelukast &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>J&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Montelukast Inhibits NF-&#954;B and Leukotriene B4 Receptor &#40;LTB4R&#41; Expression in the Lung Parenchyma</span><p id="par0045" class="elsevierStylePara elsevierViewall">In the present study&#44; increased expression of NF-&#954;B by parenchymal leukocytes for both periods studied &#40;24<span class="elsevierStyleHsp" style=""></span>h and 48<span class="elsevierStyleHsp" style=""></span>h&#41; post-LPS stimulation compared with PBS groups &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>A and B&#41; was observed&#46; The results also revealed that Montelukast efficiently reduced the NF-&#954;B expression &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B&#41;&#46; LTB4 signals mainly via LTB4R&#44; which results in the recruitment of neutrophils&#46; The present study demonstrated that LPS stimulation at 24<span class="elsevierStyleHsp" style=""></span>h and 48<span class="elsevierStyleHsp" style=""></span>h resulted in increased expression of LTB4R by parenchymal leukocytes &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>C and D&#41; while Montelukast significantly reduced the LTB4R expression &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>D&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>E&#8211;H shows representative photomicrographs of NF-kB for PBS48<span class="elsevierStyleHsp" style=""></span>h&#44; LPS24<span class="elsevierStyleHsp" style=""></span>h&#44; LPS48<span class="elsevierStyleHsp" style=""></span>h and LPS48h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>montelukast groups&#44; respectively&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Montelukast Restores VEGF Expression in LPS-injured Lungs</span><p id="par0050" class="elsevierStylePara elsevierViewall">Treatment with LPS decreased VEGF expression at 24<span class="elsevierStyleHsp" style=""></span>h &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>A&#41; and furthermore at 48<span class="elsevierStyleHsp" style=""></span>h while Montelukast administration at 24<span class="elsevierStyleHsp" style=""></span>h resulted in a recovery of VEGF expression in BAL compared to control &#40;PBS&#41; treated animals &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>B&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Montelukast Reduces IL-8 Release by Human Neutrophils</span><p id="par0055" class="elsevierStylePara elsevierViewall">Human neutrophils were stimulated with LPS &#40;1&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mL&#41; for 1<span class="elsevierStyleHsp" style=""></span>h and then incubated with Montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M in PBS&#41; for an additional 5<span class="elsevierStyleHsp" style=""></span>h&#46; ELISA for IL-8 was performed on the supernatant&#46; Montelukast treatment significantly inhibited LPS-stimulated production of IL-8 &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>A&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">The present study demonstrates for the first time that leukotriene inhibitor Montelukast reduces both acute LPS-induced lung inflammation in mice as well as LPS-induced human neutrophils activation&#46; Exacerbated inflammation plays a central role in the pathogenesis of ARDS&#59; therefore in the quest to develop effective ARDS therapies&#44; reducing inflammation has been a main goal&#46; The off-target effects of Montelukast on LTB4 receptors present on neutrophils could have beneficial implications in ARDS therapy&#46; Leukotriene B4 &#40;LTB4&#41; is synthesized primarily by activated basophils&#44; eosinophils&#44; monocytes and macrophages and acts in both an autocrine and paracrine manner by signaling to structural cells&#44; neutrophils and TH2 lymphocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">14</span></a> Though neutrophils express a low level of LTB4 receptor&#44; LTB4 acts as a strong chemoattractant of neutrophils&#44; a cell centrally involved in ARDS&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">While the recognition of the involvement of leukotriene pathways in asthma prompted the development of leukotriene receptor inhibitors&#44; drugs such as Montelukast&#44; a leukotriene inhibitor&#44; have not yet been tested in the context of ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">15</span></a> Twenty-five years ago&#44; a swine LPS model of acute lung injury &#40;ALI&#41; demonstrated that the LTBR1 competitive receptor antagonist LY255283 reduced ALI&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">16</span></a> However&#44; unlike Montelukast&#44; this agent did not exhibit potent off target anti-inflammatory effects such as the inhibition of cyclooxygenase or 5-lipoxygenase enzymes&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a> Therefore&#44; in the case of ARDS&#44; Montelukast may be an effective inhibitor of inflammation not only because of its ability to inhibit leukotriene signaling&#44; but also via off-target effects which result in a net increase in cyclic adenosine monophosphate &#40;cAMP&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> and the suppression of NF-kB<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> which leads to the attenuation of cytokine production and a dispersal of lung immune cells&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">This study used the LPS-induced acute lung injury model in mice to test the hypothesis that the Montelukast would attenuate lung inflammation&#46; Our results indicated that Montelukast reduced the LPS-induced increase in total immune cells both in the BAL&#44; suggesting decreased vascular permeability&#44; and in the lung parenchyma&#46; In addition&#44; Montelukast treated mice displayed significantly reduced levels of cytokines IL-6&#44; CXCL1&#47;KC&#44; IL-17 and TNF-&#945; suggesting attenuation of inflammatory processes due to LPS&#46; LPS-induced pulmonary dysfunction was associated with increased neutrophil count&#44; leukotriene &#40;LT&#41; B4&#44; and tumor necrosis factor &#40;TNF&#41;-&#945; in BALF&#46; These results suggest that treatment with Montelukast can be useful in chronic airway inflammatory diseases including COPD poorly responsive to glucocorticoids&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">20</span></a> In addition&#44; Montelukast treated mice also displayed reduced LTB4R and NF-&#954;B expression in the lung parenchyma&#44; which correlates to decreased leukotriene signaling and decreased inflammation and Montelukast was able to block LTD&#40;4&#41;-induced stimulation&#46; Allergen challenge leads to a significant increase in sCD14 concentrations in BAL and might modulate the allergen-induced inflammation&#46; In addition&#44; LTD&#40;4&#41; might play a role in the release of sCD14&#44; and it could be speculated that sCD14 reduction by LTRA might contribute to the mechanisms of LTRA in the treatment of allergic asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">21</span></a> Moreover&#44; LTB&#40;4&#41;- and LTD&#40;4&#41;-induced eosinophil activation was attenuated by CP-105&#44;696 and the Cys-LT&#40;1&#41; receptor antagonist montelukast&#44; respectively&#44; highlighting specific receptor dependency&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a> Thus&#44; mediator-triggered granulocyte activation and antiapoptotic pathways are distinct events that can be differentially regulated&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">22</span></a> Lastly&#44; our results presented herein indicates that Montelukast treatment resulted in a recovery of VEGF expression in the BAL&#44; a measurement which is associated with recovery in ARDS patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">23&#8211;25</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">While neutrophils themselves do not produce LTB4&#44; and LTB4 receptors are expressed only at low levels&#44; exposure to LTB4 primes neutrophils to produce copious amounts of reactive oxygen species &#40;ROS&#41;&#44; matrix metalloproteinases &#40;MMPs&#41; and other cytokines upon stimulation by additional cytokines&#46; Human neutrophils activated with the chemoattractant N-formyl-<span class="elsevierStyleSmallCaps">l</span>-methionyl-<span class="elsevierStyleSmallCaps">l</span>-leucyl-<span class="elsevierStyleSmallCaps">l</span>-phenylalanine &#40;fMLP&#41; in combination with cytochalasin B resulted in abrupt and sustained increases in cytosolic Ca<span class="elsevierStyleSup">2</span>&#40;&#43;&#41;&#44; as well as release of elastase and production of superoxide and LTB4&#44; and expression of macrophage complement receptor 3 &#40;CR3&#41;&#46; These effects were attenuated with Montelukast treatment and the literature point out its association with significant increases in cyclic AMP&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> In this study&#44; human neutrophils were stimulated with LPS which signals via TLR4 and activates NF-kB-signaling resulting in the production of cytokines&#44; particularly IL-8&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a> Stimulation with LPS for 1<span class="elsevierStyleHsp" style=""></span>h&#44; followed by one treatment of Montelukast resulted in a significant reduction of IL-8 in the cell supernatant&#46; Given the low level of LTBR4 receptor expression by neutrophils&#44; this study also suggests that an important off-target effect of Montelukast is the ability to attenuate NF-kB signaling&#44; likely through upstream mechanisms that increase intracellular cAMP&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">An interesting point that should be highlighted is the fact that our results showed herein a reduction of circulating levels of IL-17 in Montelukast-treated mice with acute lung inflammation&#46; Therefore&#44; from our results&#44; is possible suggest that the Th17 cells could be a bystander mediator of Montelukast effect in vivo&#44; since that IL-17 is produced by Th17 cells&#44; and this subset expresses high levels of LTB4R1 and CysTLR1&#44; being attracted by leukotrienes &#40;especially LTD4&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In conclusion&#44; this is the first study to report the effects of Montelukast in an LPS mouse model of ARDS and in LPS-stimulated human neutrophils activation&#46; These results concur not only the potent anti-inflammatory nature of Montelukast but also its ability to signal via LTB4R independent pathways&#46; Future studies should further explore the nature of these mechanisms especially in the context of human neutrophils&#44; a central inflammation mediator of ARDS&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Material and methods</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Experimental Design of Animal Experiments</span><p id="par0090" class="elsevierStylePara elsevierViewall">This study was approved by the ethical committee of Nove de Julho University &#40;AN0002&#47;2015&#41; and were carried out in accordance to Guide for the Care and Use of Laboratory Animals&#44; published by the U&#46;S&#46; National Institutes of Health &#40;NIH publication no&#46; 85-23&#44; revised 1996&#41;&#46; Thirty-eight C57Bl&#47;6 male mice weighing between 20 and 25<span class="elsevierStyleHsp" style=""></span>g were distributed in Control 24<span class="elsevierStyleHsp" style=""></span>h &#40;PBS24<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;&#44; LPS 24<span class="elsevierStyleHsp" style=""></span>h &#40;LPS24<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;&#44; Control 48<span class="elsevierStyleHsp" style=""></span>h &#40;PBS48<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#44; LPS 48<span class="elsevierStyleHsp" style=""></span>h &#40;LPS48<span class="elsevierStyleHsp" style=""></span>h&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41; and LPS 48<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>montelukast &#40;LPS 48<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>MK&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;&#46; For Montelukast administration&#44; animals were anesthetized by intra-peritoneal injection of ketamine &#40;100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; and xylazine &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#46; The PBS24<span class="elsevierStyleHsp" style=""></span>h and LPS24<span class="elsevierStyleHsp" style=""></span>h groups were euthanized 24<span class="elsevierStyleHsp" style=""></span>h after vehicle &#40;PBS 50<span class="elsevierStyleHsp" style=""></span>&#956;l&#41; or LPS &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mouse&#47;50<span class="elsevierStyleHsp" style=""></span>&#956;l PBS&#41; administration&#46; The PBS48<span class="elsevierStyleHsp" style=""></span>h&#44; LPS48<span class="elsevierStyleHsp" style=""></span>h and LPS 48<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>MK groups were euthanized 48<span class="elsevierStyleHsp" style=""></span>h after vehicle &#40;PBS&#59; 50<span class="elsevierStyleHsp" style=""></span>&#956;l&#41; or LPS &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mouse&#47;50<span class="elsevierStyleHsp" style=""></span>&#956;l PBS&#41; administration&#46; Montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M&#47;mouse&#47;50<span class="elsevierStyleHsp" style=""></span>&#956;l PBS&#41; was orotracheally administered 24<span class="elsevierStyleHsp" style=""></span>h after LPS administration and animals were euthanized 24<span class="elsevierStyleHsp" style=""></span>h later&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Assessment of Lung Inflammation</span><p id="par0095" class="elsevierStylePara elsevierViewall">Lung inflammation was assessed through the collection and analysis of bronchoalveolar lavage &#40;BAL&#41;&#46; Quantitative analysis of parenchymal inflammation was performed using histomorphometrical technique&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;31</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The numbers of total and differential cells in BAL were evaluated in the material recovered from 3 gentle washes of 0&#46;5<span class="elsevierStyleHsp" style=""></span>mL of sterile PBS&#44; by using a Neubauer chamber &#40;total cells&#41; and cytospin preparations &#40;differential cell count&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;31</span></a> The cytospins were stained with Diff Quick &#40;Medion Diagnostics&#44; D&#252;dingen&#44; Switzerland&#41;&#44; as previously described&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">27&#8211;32</span></a> In summary&#44; 300<span class="elsevierStyleHsp" style=""></span>cells per slide per mouse were analyzed using an optical microscope and were counted according to the classical hematological criteria&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;34</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The density of neutrophils&#44; lymphocytes and macrophages in the lung parenchyma was evaluated as previously described&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;31</span></a> Briefly&#44; the lungs were excised in block&#44; fixed in 10&#37; formalin solution&#44; at a constant pressure &#40;20<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#41; for 24<span class="elsevierStyleHsp" style=""></span>h&#44; and submitted to histological routine&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Five micrometer lung slices were stained with hematoxylin and eosin and 20 photomicrographs at 400&#215; magnification of each animal of all groups were obtained using an Olympus BX43-L-FL microscope with a camera XM-10&#46; The area of lung tissue in the lung parenchyma was obtained by subtracting the airspace area from the total photo area&#46; Then&#44; the number of neutrophils&#44; lymphocytes and macrophages were counted in each photo according to the morphological criteria&#46; The results were expressed in number of cells&#47;mm2 of lung tissue&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">30&#8211;33</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Total Proteins in BAL</span><p id="par0115" class="elsevierStylePara elsevierViewall">The levels of total proteins in BAL was measured using the BCA Protein Assay Kit &#40;Thermo Scientific&#44; USA&#41; and was used as an index of vascular permeability&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">31</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Cytokines in BAL&#44; Serum and in Cell Culture Supernatants</span><p id="par0120" class="elsevierStylePara elsevierViewall">The levels of IL-6 &#40;Biolegend&#44; Code 431306&#59; Detection limit 7&#46;8<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41;&#44; CXCL1&#47;KC &#40;R&#38;D Systems&#44; Code DY453&#59; Detection limit 15&#46;6<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41;&#44; IL-8 &#40;Biolegend&#44; Code 431506&#59; Detection limit 15&#46;6<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41;&#44; IL-17 &#40;R&#38;D Systems&#44; Code DY421&#59; Detection limit 15&#46;6<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; and TNF-&#945; &#40;Biolegend&#44; Code 430906&#59; Detection limit 7&#46;8<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; in BAL and in cell culture supernatants were measured using ELISA kits from Biolegends &#40;USA&#41; and R&#38;D Systems &#40;USA&#41; as indicated&#44; according to the manufacturers&#8217; recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> The measurements were done in triplicates in all samples&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Immunohistochemical Study</span><p id="par0125" class="elsevierStylePara elsevierViewall">The quantitative analysis of the expression of leukotriene B4 receptor &#40;LTB4R&#41; &#40;sc-98841&#59; Santa Cruz&#44; CA&#44; USA&#41; and of NF-&#954;B p65 &#40;sc-109&#59; Santa Cruz&#44; CA&#44; USA&#41; by parenchymal leukocytes was performed using classical immunohistochemistry protocol&#44; as previously described&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">30&#44;33&#44;34</span></a> Briefly&#44; the area of lung tissue in the lung parenchyma was obtained by subtracting the airspace area from the total photo area&#46; Then&#44; the number of leukocytes positive to LTB4R and NF-kB p65 were counted in each photo&#46; The results were expressed in number of positive cells&#47;mm<span class="elsevierStyleSup">2</span> of lung tissue&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;32</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Isolation and Culture of Human Neutrophils</span><p id="par0130" class="elsevierStylePara elsevierViewall">Eight milliliter of peripheral blood was diluted 1&#58;1 in sterile PBS and added to a tube containing Ficoll Paque gradient and submitted to 20<span class="elsevierStyleHsp" style=""></span>min centrifugation &#40;1200<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">g</span>&#41;&#46; Red cells were lysed&#44; polymorphonuclear cells collected and neutrophils were separated from eosinophils using EasySep&#8482; Human Neutrophil Enrichment Kit &#40;&#35;19257&#59; StemCell Technologies&#44; USA&#41;&#46; The purity was assessed through cytospin analysis and was higher than 98&#37;&#46; Neutrophils &#40;1<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">6</span>&#47;2<span class="elsevierStyleHsp" style=""></span>mL medium&#47;well&#41; were incubated in 48 well plates in RPMI 1640 medium and were stimulated with LPS &#40;1&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mL medium&#41; for 1<span class="elsevierStyleHsp" style=""></span>h and then incubated with montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M in PBS&#41; for an additional 5<span class="elsevierStyleHsp" style=""></span>h&#46; Supernatant was recovered for measurements of IL-8 by ELISA&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Statistical Analysis</span><p id="par0135" class="elsevierStylePara elsevierViewall">If not stated otherwise&#44; two-way analysis of variance &#40;TWO-WAY ANOVA&#41; followed by Bonferroni post hoc test was used&#46; Significance levels were considered for <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46; Values were expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SEM&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Authorship</span><p id="par0140" class="elsevierStylePara elsevierViewall">JEDC&#44; MCOJ&#44; BM&#44; AD&#44; ARAO&#44; JCJAJ&#44; AAB&#44; NCRO&#44; NRDR&#44; contributed performing the experiments and analysis&#46; APLO&#44; APS&#44; FMCC&#44; FA&#44; HCCFN&#44; and RPV have written the manuscript and critically revised the manuscript and performed the statistical analysis&#46; RPV have designed the study&#46; All authors have reviewed and approved the final version of the manuscript prior to submission&#46;</p></span></span>"
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          "titulo" => "Introduction"
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              "titulo" => "Montelukast Reduces Leukocyte Number in Bronchoalveolar Lavage &#40;BAL&#41;"
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              "titulo" => "Montelukast Reduces Vascular Permeability and Cytokines in Bronchoalveolar Lavage &#40;BAL&#41;"
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              "titulo" => "Montelukast Reduces Neutrophils&#44; Lymphocytes and Macrophages Accumulation in the Lung Parenchyma"
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              "titulo" => "Montelukast Inhibits NF-&#954;B and Leukotriene B4 Receptor &#40;LTB4R&#41; Expression in the Lung Parenchyma"
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              "titulo" => "Montelukast Restores VEGF Expression in LPS-injured Lungs"
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              "titulo" => "Montelukast Reduces IL-8 Release by Human Neutrophils"
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              "titulo" => "Assessment of Lung Inflammation"
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              "identificador" => "sec0065"
              "titulo" => "Total Proteins in BAL"
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              "titulo" => "Cytokines in BAL&#44; Serum and in Cell Culture Supernatants"
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              "titulo" => "Immunohistochemical Study"
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              "titulo" => "Isolation and Culture of Human Neutrophils"
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              "titulo" => "Statistical Analysis"
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          "titulo" => "Authorship"
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          "titulo" => "Acknowledgements"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2018-07-03"
    "fechaAceptado" => "2019-05-01"
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            0 => "Inflammation"
            1 => "Neutrophils"
            2 => "Acute lung injury"
            3 => "Leukotriene"
            4 => "Cytokines"
            5 => "Growth factors"
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            0 => "Inflamaci&#243;n"
            1 => "Neutr&#243;filos"
            2 => "Da&#241;o pulmonar agudo"
            3 => "Leucotrieno"
            4 => "Citoquinas"
            5 => "Factores de crecimiento"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Some pro-inflammatory lipids derived from 1 lipooxygenase enzyme are potent neutrophil chemoattractant&#44; a cell centrally involved in acute respiratory distress syndrome &#40;ARDS&#41;&#59; a syndrome lacking effective treatment&#46; Considering the beneficial effects of the leukotriene receptor inhibitor&#44; montelukast&#44; on other lung diseases&#44; whether montelukast attenuates inflammation in a mouse model of ARDS&#44; and whether it reduces LPS stimulated activation of human neutrophils was investigated&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Thirty-five C57Bl&#47;6 mice were distributed into control &#40;PBS&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h&#44; LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mouse&#41;&#44; control<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>48<span class="elsevierStyleHsp" style=""></span>h&#44; LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>48<span class="elsevierStyleHsp" style=""></span>h&#44; and LPS 48<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#46; In addition&#44; human neutrophils were incubated with LPS &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;mL&#41; and treated with montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Oral-tracheal administration of montelukast significantly attenuated total cells &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; macrophages &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; neutrophils &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#44; lymphocytes &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; and total protein levels in BAL &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; as well as IL-6 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; CXCL1&#47;KC &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; IL-17 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41; and TNF-&#945; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#46; Furthermore&#44; montelukast reduced neutrophils &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; lymphocytes &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; and macrophages &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; in the lung parenchyma&#46; In addition&#44; montelukast restored BAL VEGF levels &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#46; LTB4 receptor expression &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; as well as NF-&#954;B &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; a downstream target of LPS&#44; were also reduced in lung parenchymal leukocytes&#46; Furthermore&#44; montelukast reduced IL-8 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; production by LPS-treated human neutrophils&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In conclusion&#44; montelukast efficiently attenuated both LPS-induced lung inflammation in a mouse model of ARDS and in LPS challenged human neutrophils&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
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            "titulo" => "Conclusion"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Algunos l&#237;pidos proinflamatorios derivados de la enzima lipooxigenasa 1 son potentes quimioatrayentes de neutr&#243;filos&#44; un tipo celular con una implicaci&#243;n principal en el s&#237;ndrome de distr&#233;s respiratorio agudo &#40;SDRA&#41;&#44; para el que no hay tratamiento efectivo&#46; Considerando los efectos beneficiosos del inhibidor de los receptores de leucotrienos montelukast en otras enfermedades pulmonares&#44; se investig&#243; si este f&#225;rmaco era capaz de atenuar la inflamaci&#243;n en un modelo de rat&#243;n de SDRA y de reducir la activaci&#243;n de los neutr&#243;filos humanos inducida por LPS&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se utilizaron 35 ratones C57BL&#47;6 distribuidos en los siguientes grupos&#58; control &#40;PBS&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h&#44; LPS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#40;24<span class="elsevierStyleHsp" style=""></span>h &#91;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;rat&#243;n&#93;&#41;&#44; control<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>48<span class="elsevierStyleHsp" style=""></span>h y LPS 48<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#46; Por otro lado&#44; se incubaron neutr&#243;filos humanos con LPS &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#41; y se trataron con montelukast &#40;10<span class="elsevierStyleHsp" style=""></span>&#956;M&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La administraci&#243;n orotraqueal de montelukast redujo el n&#250;mero total de c&#233;lulas &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; de macr&#243;fagos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; de neutr&#243;filos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#44; de linfocitos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y los niveles totales de prote&#237;na en el lavado broncoalveolar &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; as&#237; como de IL-6 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; CXCL1&#47;KC &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#44; IL-17 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; 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              "identificador" => "bib0175"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute respiratory distress syndrome&#58; the Berlin Definition"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46;M&#46; Ranieri"
                            1 => "G&#46;D&#46; Rubenfeld"
                            2 => "B&#46;T&#46; Thompson"
                            3 => "N&#46;D&#46; Ferguson"
                            4 => "E&#46; Caldwell"
                            5 => "E&#46; Fan"
                          ]
                        ]
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1001/jama.2012.5669"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2012"
                        "volumen" => "307"
                        "paginaInicial" => "2526"
                        "paginaFinal" => "2533"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22797452"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An official American Thoracic Society workshop report&#58; features and measurements of experimental acute lung injury in animals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Matute-Bello"
                            1 => "G&#46; Downey"
                            2 => "B&#46;B&#46; Moore"
                            3 => "S&#46;D&#46; Groshong"
                            4 => "M&#46;A&#46; Matthay"
                            5 => "A&#46;S&#46; Slutsky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/rcmb.2009-0210ST"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2011"
                        "volumen" => "44"
                        "paginaInicial" => "725"
                        "paginaFinal" => "738"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21531958"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Silencing Angiopoietin-Like Protein 4 &#40;ANGPTL4&#41; protects against lipopolysaccharide-induced acute lung injury via regulating SIRT1&#47;NF-kB pathway"
                      "autores" => array:1 [
                        0 => array:2 [
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                          "autores" => array:6 [
                            0 => "L&#46; Guo"
                            1 => "S&#46; Li"
                            2 => "Y&#46; Zhao"
                            3 => "P&#46; Qian"
                            4 => "F&#46; Ji"
                            5 => "L&#46; Qian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jcp.24969"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cell Physiol"
                        "fecha" => "2015"
                        "volumen" => "230"
                        "paginaInicial" => "2390"
                        "paginaFinal" => "2402"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25727991"
                            "web" => "Medline"
                          ]
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                    ]
                  ]
                ]
              ]
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            3 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Magnolol ameliorates lipopolysaccharide-induced acute lung injury in rats through PPAR&#947;-dependent inhibition of NF-kB activation"
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                        0 => array:2 [
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                          "autores" => array:5 [
                            0 => "M&#46;H&#46; Lin"
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                            2 => "T&#46;H&#46; Chen"
                            3 => "H&#46;Y&#46; Chang"
                            4 => "T&#46;C&#46; Chou"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
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                      "doi" => "10.1016/j.intimp.2015.05.051"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int Immunopharmacol"
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                        "volumen" => "28"
                        "paginaInicial" => "270"
                        "paginaFinal" => "278"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26072062"
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            4 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Asef mediates HGF protective effects against LPS induced lung injury and endothelial barrier dysfunction"
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                            0 => "F&#46; Meng"
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                            5 => "T&#46; Akiyama"
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                        "tituloSerie" => "Am J Physiol Lung Cell Mol Physiol"
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                        "volumen" => "308"
                        "paginaInicial" => "L452"
                        "paginaFinal" => "L463"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25539852"
                            "web" => "Medline"
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                      "doi" => "10.1016/j.cyto.2008.01.006"
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                        "tituloSerie" => "Cytokine"
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                        "paginaFinal" => "151"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18304834"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "NF-kB binding activity in mixed Bal cells from patients with SIRS and ARDS"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;W&#46; Christman"
                            1 => "A&#46; Venkatakrishnan"
                            2 => "A&#46;P&#46; Wheeler"
                            3 => "G&#46;R&#46; Bernard"
                            4 => "T&#46;S&#46; Blackwell"
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Sepsis"
                        "fecha" => "2008"
                        "volumen" => "4"
                        "paginaInicial" => "35"
                        "paginaFinal" => "41"
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "titulo" => "NF-B family 317 of transcription factors&#58; central regulators of innate and adaptive immune functions"
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                          "etal" => false
                          "autores" => array:2 [
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                            1 => "C&#46;A&#46; Hunter"
                          ]
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                    0 => array:2 [
                      "doi" => "10.1128/cmr.15.3.414-429.2002"
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                        "tituloSerie" => "Clin Microbiol Rev"
                        "fecha" => "2002"
                        "volumen" => "15"
                        "paginaInicial" => "414"
                        "paginaFinal" => "429"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12097249"
                            "web" => "Medline"
                          ]
                        ]
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                    ]
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                ]
              ]
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              "identificador" => "bib0215"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The complexity of NF-&#954;B signaling in inflammation and cancer"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46; Hoesel"
                            1 => "J&#46;A&#46; Schmid"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Cancer"
                        "fecha" => "2013"
                        "volumen" => "2"
                        "paginaInicial" => "12"
                        "paginaFinal" => "86"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12605718"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0220"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The nuclear factor NF-kappaB pathway in inflammation"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "T&#46; Lawrence"
                          ]
                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1101/cshperspect.a001651"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cold Spring Harb Perspect Biol"
                        "fecha" => "2009"
                        "volumen" => "1"
                        "paginaInicial" => "a001651"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20457564"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nuclear factor &#40;NF&#41;-&#954;B p65 regulates differentiation of human and mouse lung fibroblasts mediated by TGF&#946;"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "X&#46; Sun"
                            1 => "E&#46; Chen"
                            2 => "R&#46; Dong"
                            3 => "W&#46; Chen"
                            4 => "Y&#46; Hu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.lfs.2014.11.033"
                      "Revista" => array:6 [
                        "tituloSerie" => "Life Sci"
                        "fecha" => "2015"
                        "volumen" => "122"
                        "paginaInicial" => "8"
                        "paginaFinal" => "14"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25498897"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Avasarala"
                            1 => "F&#46; Zhang"
                            2 => "G&#46; Liu"
                            3 => "R&#46; Wang"
                            4 => "S&#46;D&#46; London"
                            5 => "L&#46; London"
                          ]
                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0057285"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS ONE"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "e57285"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23437361"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cysteinyl leukotriene receptor-1 antagonists as modulators of innate immune cell function"
                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:6 [
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                            1 => "H&#46;C&#46; Steel"
                            2 => "G&#46;R&#46; Tintinger"
                            3 => "C&#46;M&#46; Gravett"
                            4 => "R&#46; Anderson"
                            5 => "C&#46; Feldman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2014/608930"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Immunol Res"
                        "fecha" => "2014"
                        "volumen" => "2014"
                        "paginaInicial" => "608930"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24971371"
                            "web" => "Medline"
                          ]
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                    ]
                  ]
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              "identificador" => "bib0240"
              "etiqueta" => "14"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction"
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                            4 => "B&#46;G&#46; Monks"
                            5 => "E&#46;A&#46; Kurt-Jones"
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                      ]
                    ]
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                    0 => array:2 [
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                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2002"
                        "volumen" => "277"
                        "paginaInicial" => "47834"
                        "paginaFinal" => "47843"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12324469"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0245"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Pharmacokinetics&#44; bioavailability&#44; 358 and safety of montelukast sodium &#40;MK-0476&#41; in healthy males and females"
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                        0 => array:2 [
                          "etal" => true
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                            1 => "J&#46;A&#46; Leff"
                            2 => "R&#46; Amin"
                            3 => "B&#46;J&#46; Gertz"
                            4 => "M&#46; De Smet"
                            5 => "N&#46; Noonan"
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                      "doi" => "10.1023/a:1016056912698"
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                        "tituloSerie" => "Pharm Res"
                        "fecha" => "1996"
                        "volumen" => "13"
                        "paginaInicial" => "445"
                        "paginaFinal" => "448"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8692739"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0250"
              "etiqueta" => "16"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "LY255283&#44; a novel leukotriene B4 receptor antagonist&#44; limits activation of neutrophils and prevents acute lung injury induced by endotoxin in pigs"
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                            3 => "H&#46; Wang"
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                            5 => "M&#46;P&#46; Fink"
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
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                        "paginaInicial" => "191"
                        "paginaFinal" => "198"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8393594"
                            "web" => "Medline"
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                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0255"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Pulmonary actions of LY255283&#44; a leukotriene B4 receptor antagonist"
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                            2 => "S&#46;L&#46; Cockerham"
                            3 => "C&#46;R&#46; Roman"
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                            5 => "S&#46;M&#46; Spaethe"
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                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Pharmacol"
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                        "paginaInicial" => "57"
                        "paginaFinal" => "64"
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0260"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Cyclic AMP mediated inhibition of 5-lipoxygenase translocation and leukotriene biosynthesis in human neutrophils"
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                            4 => "P&#46; Borgeat"
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                    0 => array:2 [
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                        "paginaInicial" => "250"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12130675"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Inhibition of the NFkappaB transcriptional activity by protein kinase A"
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                        ]
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                    ]
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                    0 => array:2 [
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                        "tituloSerie" => "Eur J Biochem"
                        "fecha" => "2002"
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                        "paginaInicial" => "4559"
                        "paginaFinal" => "4565"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12230568"
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              "identificador" => "bib0270"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Montelukast versus dexamethasone treatment in a guinea pig model of chronic pulmonary neutrophilic inflammation"
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                        "tituloSerie" => "COPD"
                        "fecha" => "2016"
                        "volumen" => "13"
                        "paginaInicial" => "455"
                        "paginaFinal" => "463"
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                          0 => array:2 [
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                          "etal" => false
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                    ]
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                        "tituloSerie" => "Scand J Immunol"
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                        "paginaFinal" => "311"
                        "link" => array:1 [
                          0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Role of leukotrienes in the regulation of human granulocyte behaviour&#58; dissociation between agonist-induced activation and retardation of apoptosis"
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                        "tituloSerie" => "Br J Pharmacol"
                        "fecha" => "2003"
                        "volumen" => "139"
                        "paginaInicial" => "388"
                        "paginaFinal" => "398"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12770944"
                            "web" => "Medline"
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                ]
              ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Vascular endothelial 337 growth factor &#40;VEGF&#41; in acute lung injury &#40;ALI&#41; and acute respiratory distress syndrome &#40;ARDS&#41;&#58; paradox or paradigm&#63;"
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                        0 => array:2 [
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                        "tituloSerie" => "Thorax"
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                        "volumen" => "61"
                        "paginaInicial" => "621"
                        "paginaFinal" => "626"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16807391"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury"
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                          "etal" => true
                          "autores" => array:6 [
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                            2 => "D&#46; Jean"
                            3 => "M&#46; Gouge"
                            4 => "L&#46; Brochard"
                            5 => "B&#46; Housset"
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                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.01.00074701"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2001"
                        "volumen" => "18"
                        "paginaInicial" => "100"
                        "paginaFinal" => "106"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11510779"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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                    0 => array:2 [
                      "titulo" => "A role for vascular endothelial growth factor in acute and resolving lung injury"
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                            2 => "A&#46;B&#46; Millar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.2105057"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2002"
                        "volumen" => "166"
                        "paginaInicial" => "1332"
                        "paginaFinal" => "1337"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12421742"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interactive inhibitory effects of formoterol and montelukast on activated human neutrophils"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;M&#46; Gravett"
                            1 => "A&#46;J&#46; Theron"
                            2 => "H&#46;C&#46; Steel"
                            3 => "G&#46;R&#46; Tintinger"
                            4 => "R&#46; Cockeran"
                            5 => "C&#46; Feldman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00157409"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2010"
                        "volumen" => "36"
                        "paginaInicial" => "1417"
                        "paginaFinal" => "1424"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20413544"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Essential involvement of interleukin-8 &#40;IL-8&#41; in acute inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Harada"
                            1 => "N&#46; Sekido"
                            2 => "T&#46; Akahoshi"
                            3 => "T&#46; Wada"
                            4 => "N&#46; Mukaida"
                            5 => "K&#46; Matsushima"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Leukoc Biol"
                        "fecha" => "1994"
                        "volumen" => "56"
                        "paginaInicial" => "559"
                        "paginaFinal" => "564"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7964163"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Leukotrienes induce the migration of Th17 cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "W&#46; Lee"
                            1 => "H&#46; Su Kim"
                            2 => "G&#46;R&#46; Lee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/icb.2014.104"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunol Cell Biol"
                        "fecha" => "2015"
                        "volumen" => "93"
                        "paginaInicial" => "472"
                        "paginaFinal" => "479"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25512344"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low-intensity swimming training partially inhibits lipopolysaccharide-induced acute lung injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;S&#46; Ramos"
                            1 => "C&#46;R&#46; Olivo"
                            2 => "F&#46;D&#46; Quirino Santos Lopes"
                            3 => "A&#46;C&#46; Toledo"
                            4 => "M&#46;A&#46; Martins"
                            5 => "R&#46;A&#46; Lazo Os&#243;rio"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1249/MSS.0b013e3181ad1c72"
                      "Revista" => array:6 [
                        "tituloSerie" => "Med Sci Sports Exerc"
                        "fecha" => "2010"
                        "volumen" => "42"
                        "paginaInicial" => "113"
                        "paginaFinal" => "119"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20010123"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protective effects of aerobic exercise on acute lung injury induced by LPS in mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;C&#46;T&#46; Reis"
                            1 => "G&#46;C&#46;G&#46; Reis"
                            2 => "F&#46;M&#46; de Almeida"
                            3 => "F&#46;D&#46; Lopes"
                            4 => "D&#46;A&#46;C&#46; dos Santos"
                            5 => "F&#46;A&#46; dos Santos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2012"
                        "volumen" => "18"
                        "paginaInicial" => "R199"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low level laser therapy reduces acute lung inflammation in a model of pulmonary and extrapulmonary LPS-induced ARDS"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;C&#46; Oliveira Jr&#46;"
                            1 => "F&#46;R&#46; Greiffo"
                            2 => "N&#46;C&#46; Rigonato-Oliveira"
                            3 => "R&#46;W&#46; Cust&#243;dio"
                            4 => "V&#46;R&#46; Silva"
                            5 => "N&#46;R&#46; Damaceno-Rodrigues"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Photochem Photobiol B"
                        "fecha" => "2014"
                        "volumen" => "5"
                        "paginaInicial" => "57"
                        "paginaFinal" => "63"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Baudi&#223;"
                            1 => "C&#46;K&#46; Ayata"
                            2 => "Z&#46; Lazar"
                            3 => "S&#46; Cicko"
                            4 => "J&#46; Beckert"
                            5 => "A&#46; Meyer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.00080014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2015"
                        "volumen" => "45"
                        "paginaInicial" => "1669"
                        "paginaFinal" => "1680"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25614161"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Aerobic conditioning and allergic pulmonary inflammation in mice II&#46; Effects on lung vascular and parenchymal inflammation and remodeling"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;P&#46; Vieira"
                            1 => "V&#46;F&#46; de Andrade"
                            2 => "A&#46;C&#46; Duarte"
                            3 => "A&#46;B&#46; Dos Santos"
                            4 => "T&#46; Mauad"
                            5 => "M&#46;A&#46; Martins"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajplung.00465.2007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Lung Cell Mol Physiol"
                        "fecha" => "2008"
                        "volumen" => "295"
                        "paginaInicial" => "L670"
                        "paginaFinal" => "L679"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18757522"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-inflammatory effects of aerobic exercise in mice exposed to air pollution"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;P&#46; Vieira"
                            1 => "A&#46;C&#46; Toledo"
                            2 => "L&#46;B&#46; Silva"
                            3 => "F&#46;M&#46; Almeida"
                            4 => "N&#46;R&#46; Damaceno-Rodrigues"
                            5 => "E&#46;G&#46; Caldini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1249/MSS.0b013e31824b2877"
                      "Revista" => array:6 [
                        "tituloSerie" => "Med Sci Sports Exerc"
                        "fecha" => "2012"
                        "volumen" => "44"
                        "paginaInicial" => "1227"
                        "paginaFinal" => "1234"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22297803"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
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        "texto" => "<p id="par0145" class="elsevierStylePara elsevierViewall">This study was supported by <span class="elsevierStyleGrantSponsor" id="gs1">Sao Paulo Research Foundation &#40;FAPESP&#41;</span>&#44; grant <span class="elsevierStyleGrantNumber" refid="gs1">2012&#47;15165-2</span>&#46; MCOJ holds a PhD fellowship from <span class="elsevierStyleGrantSponsor" id="gs2">FAPESP</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs2">2014&#47;14604-8</span>&#41;&#46; BM holds a postdoctoral fellowship from <span class="elsevierStyleGrantSponsor" id="gs3">FAPESP</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs3">2014&#47;23196-0</span>&#41;&#46; ARAO holds a MSc fellowship from <span class="elsevierStyleGrantSponsor" id="gs4">FAPESP</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs4">2014&#47;07500-1</span>&#41;&#46; JCJAJ holds a MSc fellowship from <span class="elsevierStyleGrantSponsor" id="gs5">FAPESP</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs5">2014&#47;12755-9</span>&#41;&#46; APB holds a MSc fellowship from <span class="elsevierStyleGrantSponsor" id="gs6">CAPES</span>&#46; NCRO holds a PhD fellowship from CAPES&#46;</p>"
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ISSN: 15792129
Original language: English
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