array:23 [
  "pii" => "S1579212909734846"
  "issn" => "15792129"
  "doi" => "10.1016/S1579-2129(09)73484-6"
  "estado" => "S300"
  "fechaPublicacion" => "2009-09-01"
  "aid" => "73484"
  "copyright" => "Sociedad Española de Neumología y Cirugía Torácica"
  "copyrightAnyo" => "2009"
  "documento" => "article"
  "crossmark" => 0
  "subdocumento" => "fla"
  "cita" => "Arch Bronconeumol. 2009;45:422-8"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 2673
    "formatos" => array:3 [
      "EPUB" => 81
      "HTML" => 1954
      "PDF" => 638
    ]
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S1579212909734858"
    "issn" => "15792129"
    "doi" => "10.1016/S1579-2129(09)73485-8"
    "estado" => "S300"
    "fechaPublicacion" => "2009-09-01"
    "aid" => "73485"
    "copyright" => "Sociedad Española de Neumología y Cirugía Torácica"
    "documento" => "article"
    "crossmark" => 0
    "subdocumento" => "fla"
    "cita" => "Arch Bronconeumol. 2009;45:429-34"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 2482
      "formatos" => array:3 [
        "EPUB" => 92
        "HTML" => 1714
        "PDF" => 676
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
      "titulo" => "Asbestos-Related Diseases in a Population Near a Fibrous Cement Factory"
      "tienePdf" => "en"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "429"
          "paginaFinal" => "434"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Enfermedad por amianto en una poblaci&#243;n &#96;pr&#243;xima a una f&#225;brica de fibrocemento"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Josep Tarr&#233;s, Rafael Ab&#243;s-Herr&#224;ndiz, Constan&#231;a Albert&#237;, Xavier Mart&#237;nez-Art&#233;s, Magdalena Rosell-Murphy, Isabel Garc&#237;a-Allas, Illona Krier, Emilia Castro, Gloria Cantarell, Miguel Gallego, Ramon Orriols"
          "autores" => array:11 [
            0 => array:2 [
              "nombre" => "Josep"
              "apellidos" => "Tarr&#233;s"
            ]
            1 => array:2 [
              "nombre" => "Rafael"
              "apellidos" => "Ab&#243;s-Herr&#224;ndiz"
            ]
            2 => array:2 [
              "nombre" => "Constan&#231;a"
              "apellidos" => "Albert&#237;"
            ]
            3 => array:2 [
              "nombre" => "Xavier"
              "apellidos" => "Mart&#237;nez-Art&#233;s"
            ]
            4 => array:2 [
              "nombre" => "Magdalena"
              "apellidos" => "Rosell-Murphy"
            ]
            5 => array:2 [
              "nombre" => "Isabel"
              "apellidos" => "Garc&#237;a-Allas"
            ]
            6 => array:2 [
              "nombre" => "Illona"
              "apellidos" => "Krier"
            ]
            7 => array:2 [
              "nombre" => "Emilia"
              "apellidos" => "Castro"
            ]
            8 => array:2 [
              "nombre" => "Gloria"
              "apellidos" => "Cantarell"
            ]
            9 => array:2 [
              "nombre" => "Miguel"
              "apellidos" => "Gallego"
            ]
            10 => array:2 [
              "nombre" => "Ramon"
              "apellidos" => "Orriols"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212909734858?idApp=UINPBA00003Z"
    "url" => "/15792129/0000004500000009/v1_201305150430/S1579212909734858/v1_201305150430/en/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S1579212909734834"
    "issn" => "15792129"
    "doi" => "10.1016/S1579-2129(09)73483-4"
    "estado" => "S300"
    "fechaPublicacion" => "2009-09-01"
    "aid" => "73483"
    "copyright" => "Sociedad Espa&#241;ola de Neumolog&#237;a y Cirug&#237;a Tor&#225;cica"
    "documento" => "simple-article"
    "crossmark" => 0
    "subdocumento" => "edi"
    "cita" => "Arch Bronconeumol. 2009;45:419-21"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 1858
      "formatos" => array:3 [
        "EPUB" => 79
        "HTML" => 1203
        "PDF" => 576
      ]
    ]
    "en" => array:8 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>"
      "titulo" => "Again an asthma model&#58; but a useful one"
      "tienePdf" => "en"
      "tieneTextoCompleto" => 0
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "419"
          "paginaFinal" => "421"
        ]
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Rosa Torres, C&#233;sar Picado, Fernando de Mora"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Rosa"
              "apellidos" => "Torres"
            ]
            1 => array:2 [
              "nombre" => "C&#233;sar"
              "apellidos" => "Picado"
            ]
            2 => array:2 [
              "nombre" => "Fernando"
              "apellidos" => "de Mora"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212909734834?idApp=UINPBA00003Z"
    "url" => "/15792129/0000004500000009/v1_201305150430/S1579212909734834/v1_201305150430/en/main.assets"
  ]
  "en" => array:15 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>"
    "titulo" => "Development of a Murine Model of Airway Inflammation and Remodeling in Experimental Asthma"
    "tieneTextoCompleto" => 0
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "422"
        "paginaFinal" => "428"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Rebeca Fraga-Iriso, Laura N&#250;&#241;ez-Naveira, Nadia S&#46; Brienza, Alberto Centeno-Cort&#233;s, Eduardo L&#243;pez-Pel&#225;ez, H&#233;ctor Verea, David Ramos-Barb&#243;n"
        "autores" => array:7 [
          0 => array:2 [
            "nombre" => "Rebeca"
            "apellidos" => "Fraga-Iriso"
          ]
          1 => array:2 [
            "nombre" => "Laura"
            "apellidos" => "N&#250;&#241;ez-Naveira"
          ]
          2 => array:2 [
            "nombre" => "Nadia S&#46;"
            "apellidos" => "Brienza"
          ]
          3 => array:2 [
            "nombre" => "Alberto"
            "apellidos" => "Centeno-Cort&#233;s"
          ]
          4 => array:2 [
            "nombre" => "Eduardo"
            "apellidos" => "L&#243;pez-Pel&#225;ez"
          ]
          5 => array:2 [
            "nombre" => "H&#233;ctor"
            "apellidos" => "Verea"
          ]
          6 => array:4 [
            "nombre" => "David"
            "apellidos" => "Ramos-Barb&#243;n"
            "email" => array:1 [
              0 => "David&#46;Ramos&#46;Barbon&#64;sergas&#46;es"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">¿</span>"
                "identificador" => "cor1"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:1 [
            "entidad" => "Unidad de Investigaci&#243;n Respiratoria&#44; Servicio de Neumolog&#237;a&#44; Complejo Hospitalario Universitario&#44; Instituto de Investigaci&#243;n Biom&#233;dica de A Coru&#241;a &#40;INIBIC&#41;&#44; A Coru&#241;a&#44; Spain"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor1"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Desarrollo de un modelo murino de inflamaci&#243;n y remodelaci&#243;n de v&#237;as respiratorias en asma experimental"
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2008-07-27"
    "fechaAceptado" => "2009-01-21"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec155807"
          "palabras" => array:9 [
            0 => "Asthma"
            1 => "Animal disease models"
            2 => "Inflammation"
            3 => "Goblet cells"
            4 => "Eosinophils"
            5 => "Lymphocytes"
            6 => "Mast cells"
            7 => "Smooth muscle"
            8 => "Extracellular matrix"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec155806"
          "palabras" => array:9 [
            0 => "Asma"
            1 => "Modelos animales de enfermedad"
            2 => "Inflamaci&#243;n"
            3 => "C&#233;lulas caliciformes"
            4 => "Eosin&#243;filos"
            5 => "Linfocitos"
            6 => "Mastocitos"
            7 => "M&#250;sculo liso"
            8 => "Matriz extracelular"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Background and Objective</span><p class="elsevierStyleSimplePara elsevierViewall">Experimental animal models are necessary for studying asthma disease mechanisms and for identifying new therapeutic targets&#46; We present a murine model of experimental asthma that allows integrated&#44; quantitative assessment of airway inflammation and remodeling&#46;</p> <span class="elsevierStyleSectionTitle">Material and Methods</span><p class="elsevierStyleSimplePara elsevierViewall">BALB&#47;c mice were sensitized to ovalbumin &#40;OVA&#41; and challenged with OVA or vehicle 3 times per week for 12 weeks&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">On bronchoalveolar lavage&#44; the OVA-sensitized mice had significantly higher total leukocyte counts&#44; with a median &#40;Q25-Q75&#41; of 670&#46;0 cells&#47;mL&#215;10<span class="elsevierStyleSup">-3</span> &#40;376&#46;2-952&#46;5&#41; in comparison with 40&#46;0 cells&#47; mL&#215;10<span class="elsevierStyleSup">-3</span> &#40;60&#46;0-85&#46;0&#41; in controls &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;001&#41;&#44; and higher eosinophil and differential lymphocyte counts&#46; In sagittal sections of lungs inflated to a standard pressure&#44; the OVA-sensitized animals showed goblet cell hyperplasia in the respiratory epithelium &#40;periodic acid-Schiff staining&#44; 53&#46;89 &#91;36&#46;26-62&#46;84&#93; cells&#47;mm<span class="elsevierStyleSup">2</span> vs 0&#46;66 &#91;0&#46;00-1&#46;06&#93; cells&#47;mm<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#44; dense mononuclear and eosinophilic inflammatory infiltrates &#40;hematoxylin-eosin&#44; 32&#46;87 &#91;27&#46;34-37&#46;13&#93; eosinophils&#47;mm<span class="elsevierStyleSup">2</span> vs 0&#46;06 &#91;0&#46;00-0&#46;20&#93; eosinophils&#47;mm<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">P</span>&#61;&#46;002&#41;&#44; subepithelial infiltration by mast cells &#40;toluidine blue&#44; 2&#46;88 &#91;2&#46;00-3&#46;28&#93; mast cells&#47;mm<span class="elsevierStyleSup">2</span> vs 0&#46;28 &#91;0&#46;15-0&#46;35&#93; mast cells&#47;mm<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#44; increased contractile tissue mass &#40;immunofluorescence analysis for &#945;-smooth-muscle actin&#44; 2&#46;60 &#91;2&#46;28-2&#46;98&#93; vs 1&#46;08 &#91;0&#46;93-1&#46;16&#93;&#44; dimensionless&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41; and enhanced extracellular matrix deposition &#40;Masson&#39;s trichrome&#44; 2&#46;18 &#91;1&#46;85-2&#46;80&#93; vs 0&#46;50 &#91;0&#46;37-0&#46;65&#93;&#44; dimensionless&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">Our dataset describes an experimental model of asthma which is driven by prolonged allergen exposure and in which airway inflammation and remodeling develop and are assessed together&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p class="elsevierStyleSimplePara elsevierViewall">La investigaci&#243;n de los mecanismos de enfermedad del asma y la identificaci&#243;n de nuevas dianas terap&#233;uticas requieren modelos animales experimentales&#46; En este trabajo presentamos los datos del desarrollo de un modelo murino de asma experimental que permite valorar de forma conjunta par&#225;metros de inflamaci&#243;n y remodelaci&#243;n de las v&#237;as respiratorias mediante morfolog&#237;a cuantitativa&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todos</span><p class="elsevierStyleSimplePara elsevierViewall">Se sensibiliz&#243; a ovoalb&#250;mina a ratones Balb&#47;c y se les realiz&#243; broncoprovocaci&#243;n con ovoalb&#250;mina o excipiente 3 veces por semana durante 12 semanas&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">En el lavado broncoalveolar&#44; los ratones del grupo de ovoalb&#250;mina presentaron un incremento significativo de leucocitos totales&#44; con una mediana &#40;cuartiles 25&#8211;75&#41; de 670&#44;0 c&#233;lulas&#47;ml&#183;10<span class="elsevierStyleSup">3</span> &#40;376&#44;2&#8211;952&#44;5&#41;&#44; frente a 40&#44;0 c&#233;lulas&#47;ml&#183;10<span class="elsevierStyleSup">3</span> &#40;60&#44;0&#8211;85&#44;0&#41; en controles &#40;p &#61; 0&#44;001&#41;&#44; y de las fracciones eosin&#243;fila y linfocitaria en recuento diferencial&#46; En secciones sagitales de los pulmones inflados a presi&#243;n estandarizada&#44; estos ratones mostraron hiperplasia de c&#233;lulas caliciformes en el epitelio respiratorio &#8212;reacci&#243;n de &#225;cido pery&#243;dico de Schiff&#58; 53&#44;89 &#40;36&#44;26&#8212;62&#44;84&#41; frente a 0&#44;66 &#40;0&#44;00&#8211;1&#44;06&#41; c&#233;lulas&#47;mm<span class="elsevierStyleSup">2</span> &#40;p &#60; 0&#44;001&#41;&#8212;&#44; densa infiltraci&#243;n inflamatoria mononuclear y eosin&#243;fila &#8212;hematoxilina-eosina&#58; 32&#44;87 &#40;27&#44;34&#8211;37&#44;13&#41; frente a 0&#44;06 &#40;0&#44;00&#8211;0&#44;20&#41; eosin&#243;filos&#47;mm<span class="elsevierStyleSup">2</span> &#40;p &#61; 0&#44;002&#41;&#8212;&#44; infiltraci&#243;n subepitelial por mastocitos &#8212;azul de toluidina&#58; 2&#44;88 &#40;2&#44;00&#8211;3&#44;28&#41; frente a 0&#44;28 &#40;0&#44;15&#8211;0&#44;35&#41; mastocitos&#47;mm<span class="elsevierStyleSup">2</span> &#40;p &#60; 0&#44;001&#41;&#8212;&#44; incremento de la masa de tejido contr&#225;ctil &#8212;inmunofluorescencia para alfaactina de m&#250;sculo liso&#58; 2&#44;60 &#40;2&#44;28&#8211;2&#44;98&#41; frente a 1&#44;08 &#40;0&#44;93&#8211;1&#44;16&#41;&#44; adimensional &#40;p&#60;0&#44;001&#41;&#8212; e incremento del dep&#243;sito de matriz extracelular &#40;tricr&#243;mico de Masson&#58; 2&#44;18 &#40;1&#44;85&#8211;2&#44;80&#41; frente a 0&#44;50 &#40;0&#44;37&#8211;0&#44;65&#41;&#44; adimensional &#40;p &#60; 0&#44;001&#41;&#8212;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">Los datos aportados configuran un modelo de asma experimental inducida por exposici&#243;n alerg&#233;nica prolongada&#44; con desarrollo y evaluaci&#243;n integrada de inflamaci&#243;n y remodelaci&#243;n de v&#237;as respiratorias&#46;</p>"
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:1 [
          "bibliografiaReferencia" => array:20 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The global burden of asthma&#58; executive summary of the GINA Dissemination Committee report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Masoli"
                            1 => "D&#46; Fabian"
                            2 => "S&#46; Holt"
                            3 => "R&#46; Beasley"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1398-9995.2004.00526.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy"
                        "fecha" => "2004"
                        "volumen" => "59"
                        "paginaInicial" => "469"
                        "paginaFinal" => "478"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15080825"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Investigaci&#243;n b&#225;sica en asma&#58; &#191;hacia d&#243;nde nos dirigimos&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46; Ramos-Barb&#243;n"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2006"
                        "volumen" => "42"
                        "paginaInicial" => "613"
                        "paginaFinal" => "615"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17178063"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Modelos experimentales de asma&#46; Aportaciones y limitaciones"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Cortijo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2003"
                        "volumen" => "39"
                        "paginaInicial" => "54"
                        "paginaFinal" => "56"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12586043"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Airway remodeling&#58; lessons from animal models"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46; Ramos-Barb&#243;n"
                            1 => "M&#46;S&#46; Ludwig"
                            2 => "J&#46;G&#46; Martin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1385/CRIAI:27:1:003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Rev Allergy Immunol"
                        "fecha" => "2004"
                        "volumen" => "27"
                        "paginaInicial" => "3"
                        "paginaFinal" => "22"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15347847"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Descubriendo el asma de origen al&#233;rgico a trav&#233;s del rat&#243;n&#46; Un repaso a la patogenia de los modelos de asma al&#233;rgica en el rat&#243;n y su similitud con el asma al&#233;rgica humana"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46; Torres"
                            1 => "C&#46; Picado"
                            2 => "F&#46; De Mora"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2005"
                        "volumen" => "41"
                        "paginaInicial" => "141"
                        "paginaFinal" => "152"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15766467"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The use of the internal perimeter to compare airway size and to calculate smooth muscle shortening"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;L&#46; James"
                            1 => "J&#46;C&#46; Hogg"
                            2 => "L&#46;A&#46; Dunn"
                            3 => "P&#46;D&#46; Pare"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm/138.1.136"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am Rev Respir Dis"
                        "fecha" => "1988"
                        "volumen" => "138"
                        "paginaInicial" => "136"
                        "paginaFinal" => "139"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3202392"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transfer of allergic airway responses with serum and lymphocytes from rats sensitized to dust mite"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;L&#46; Lambert"
                            1 => "D&#46;W&#46; Winsett"
                            2 => "D&#46;L&#46; Costa"
                            3 => "M&#46;K&#46; Selgrade"
                            4 => "M&#46;I&#46; Gilmour"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.157.6.9704057"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1998"
                        "volumen" => "157"
                        "paginaInicial" => "1991"
                        "paginaFinal" => "1999"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9620937"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;R&#46; Johnson"
                            1 => "R&#46;E&#46; Wiley"
                            2 => "R&#46; Fattouh"
                            3 => "F&#46;K&#46; Swirski"
                            4 => "B&#46;U&#46; Gajewska"
                            5 => "A&#46;J&#46; Coyle"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200308-1094OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2004"
                        "volumen" => "169"
                        "paginaInicial" => "378"
                        "paginaFinal" => "385"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14597485"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of GM-CSF on immune&#44; inflammatory&#44; and clinical responses to ragweed in a novel mouse model of mucosal sensitization"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;C&#46; Cates"
                            1 => "B&#46;U&#46; Gajewska"
                            2 => "S&#46; Goncharova"
                            3 => "D&#46; &#193;lvarez"
                            4 => "R&#46; Fattouh"
                            5 => "A&#46;J&#46; Coyle"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2003"
                        "volumen" => "111"
                        "paginaInicial" => "1076"
                        "paginaFinal" => "1086"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12743573"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Induction by antigen of intrathymic apoptosis of CD4&#43;CD8&#43;TCRlo thymocytes in vivo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46;M&#46; Murphy"
                            1 => "A&#46;B&#46; Heimberger"
                            2 => "D&#46;Y&#46; Loh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "1990"
                        "volumen" => "250"
                        "paginaInicial" => "1720"
                        "paginaFinal" => "1723"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2125367"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of specific IgE responses in mice by pre-exposure to inhaled antigen"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46;G&#46; Holt"
                            1 => "J&#46;E&#46; Batty"
                            2 => "K&#46;J&#46; Turner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Immunology"
                        "fecha" => "1981"
                        "volumen" => "42"
                        "paginaInicial" => "409"
                        "paginaFinal" => "417"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7203528"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0300893211007329"
                          "estado" => "S300"
                          "issn" => "03008932"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Down-regulation of immune responses to inhaled antigen&#58; studies on the mechanism of induced suppression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;D&#46; Sedgwick"
                            1 => "P&#46;G&#46; Holt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunology"
                        "fecha" => "1985"
                        "volumen" => "56"
                        "paginaInicial" => "635"
                        "paginaFinal" => "642"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2934319"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic exposure to innocuous antigen in sensitized mice leads to suppressed airway eosinophilia that is reversed by granulocyte macrophage colony-stimulating factor"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "F&#46;K&#46; Swirski"
                            1 => "D&#46; Sajic"
                            2 => "C&#46;S&#46; Robbins"
                            3 => "B&#46;U&#46; Gajewska"
                            4 => "M&#46; Jordana"
                            5 => "M&#46;R&#46; Stampfli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2002"
                        "volumen" => "169"
                        "paginaInicial" => "3499"
                        "paginaFinal" => "3506"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12244139"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An improved murine model of asthma&#58; selective airway inflammation&#44; epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46; Temelkovski"
                            1 => "S&#46;P&#46; Hogan"
                            2 => "D&#46;P&#46; Shepherd"
                            3 => "P&#46;S&#46; Foster"
                            4 => "R&#46;K&#46; Kumar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "1998"
                        "volumen" => "53"
                        "paginaInicial" => "849"
                        "paginaFinal" => "856"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10193371"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prolonged allergen challenge in mice leads to persistent airway remodelling"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;J&#46; McMillan"
                            1 => "C&#46;M&#46; Lloyd"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Allergy"
                        "fecha" => "2004"
                        "volumen" => "34"
                        "paginaInicial" => "497"
                        "paginaFinal" => "507"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15005746"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Eosinophilic rhinitis accompanies the development of lower airway inflammation and hyper-reactivity in sensitized mice exposed to aerosolized allergen"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P&#46;W&#46; Hellings"
                            1 => "E&#46;M&#46; Hessel"
                            2 => "J&#46;J&#46; Van Den Oord"
                            3 => "A&#46; Kasran"
                            4 => "P&#46; Van Hecke"
                            5 => "J&#46;L&#46; Ceuppens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Allergy"
                        "fecha" => "2001"
                        "volumen" => "31"
                        "paginaInicial" => "782"
                        "paginaFinal" => "790"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11422139"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mouse models of global airway allergy&#58; what have we learned and what should we do next&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46;W&#46; Hellings"
                            1 => "J&#46;L&#46; Ceuppens"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1398-9995.2004.00549.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy"
                        "fecha" => "2004"
                        "volumen" => "59"
                        "paginaInicial" => "914"
                        "paginaFinal" => "919"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15291897"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mast-cell infiltration of airway smooth muscle in asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46;E&#46; Brightling"
                            1 => "P&#46; Bradding"
                            2 => "F&#46;A&#46; Symon"
                            3 => "S&#46;T&#46; Holgate"
                            4 => "A&#46;J&#46; Wardlaw"
                            5 => "I&#46;D&#46; Pavord"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa012705"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2002"
                        "volumen" => "346"
                        "paginaInicial" => "1699"
                        "paginaFinal" => "1705"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12037149"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antigen-specific CD4&#43; T cells drive airway smooth muscle remodeling in experimental asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46; Ramos-Barb&#243;n"
                            1 => "J&#46;F&#46; Presley"
                            2 => "Q&#46;A&#46; Hamid"
                            3 => "E&#46;D&#46; Fixman"
                            4 => "J&#46;G&#46; Martin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI19711"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2005"
                        "volumen" => "115"
                        "paginaInicial" => "1580"
                        "paginaFinal" => "1589"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15902312"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S021391111100389X"
                          "estado" => "S300"
                          "issn" => "02139111"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Heaves&#44; an asthma-like equine disease&#44; involves airway smooth muscle remodeling"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "B&#46; Herszberg"
                            1 => "D&#46; Ramos-Barb&#243;n"
                            2 => "M&#46; Tamaoka"
                            3 => "J&#46;G&#46; Martin"
                            4 => "J&#46;P&#46; Lavoie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2006.03.044"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2006"
                        "volumen" => "118"
                        "paginaInicial" => "382"
                        "paginaFinal" => "388"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16890762"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/15792129/0000004500000009/v1_201305150430/S1579212909734846/v1_201305150430/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "9374"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original Articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/15792129/0000004500000009/v1_201305150430/S1579212909734846/v1_201305150430/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212909734846?idApp=UINPBA00003Z"
]
Share
Journal Information
Vol. 45. Issue 9.
Pages 422-428 (September 2009)
Share
Share
Download PDF
More article options
Vol. 45. Issue 9.
Pages 422-428 (September 2009)
Original Article
Full text access
Development of a Murine Model of Airway Inflammation and Remodeling in Experimental Asthma
Desarrollo de un modelo murino de inflamación y remodelación de vías respiratorias en asma experimental
Visits
5367
Rebeca Fraga-Iriso, Laura Núñez-Naveira, Nadia S. Brienza, Alberto Centeno-Cortés, Eduardo López-Peláez, Héctor Verea, David Ramos-Barbón
Corresponding author
David.Ramos.Barbon@sergas.es

Corresponding author.
Unidad de Investigación Respiratoria, Servicio de Neumología, Complejo Hospitalario Universitario, Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, Spain
This item has received
Article information
Abstract
Background and Objective

Experimental animal models are necessary for studying asthma disease mechanisms and for identifying new therapeutic targets. We present a murine model of experimental asthma that allows integrated, quantitative assessment of airway inflammation and remodeling.

Material and Methods

BALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks.

Results

On bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25-Q75) of 670.0 cells/mL×10-3 (376.2-952.5) in comparison with 40.0 cells/ mL×10-3 (60.0-85.0) in controls (P=.001), and higher eosinophil and differential lymphocyte counts. In sagittal sections of lungs inflated to a standard pressure, the OVA-sensitized animals showed goblet cell hyperplasia in the respiratory epithelium (periodic acid-Schiff staining, 53.89 [36.26-62.84] cells/mm2 vs 0.66 [0.00-1.06] cells/mm2, P<.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34-37.13] eosinophils/mm2 vs 0.06 [0.00-0.20] eosinophils/mm2, P=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00-3.28] mast cells/mm2 vs 0.28 [0.15-0.35] mast cells/mm2, P<.001), increased contractile tissue mass (immunofluorescence analysis for α-smooth-muscle actin, 2.60 [2.28-2.98] vs 1.08 [0.93-1.16], dimensionless, P<.001) and enhanced extracellular matrix deposition (Masson's trichrome, 2.18 [1.85-2.80] vs 0.50 [0.37-0.65], dimensionless, P<.001).

Conclusions

Our dataset describes an experimental model of asthma which is driven by prolonged allergen exposure and in which airway inflammation and remodeling develop and are assessed together.

Keywords:
Asthma
Animal disease models
Inflammation
Goblet cells
Eosinophils
Lymphocytes
Mast cells
Smooth muscle
Extracellular matrix
Resumen
Introducción

La investigación de los mecanismos de enfermedad del asma y la identificación de nuevas dianas terapéuticas requieren modelos animales experimentales. En este trabajo presentamos los datos del desarrollo de un modelo murino de asma experimental que permite valorar de forma conjunta parámetros de inflamación y remodelación de las vías respiratorias mediante morfología cuantitativa.

Material y métodos

Se sensibilizó a ovoalbúmina a ratones Balb/c y se les realizó broncoprovocación con ovoalbúmina o excipiente 3 veces por semana durante 12 semanas.

Resultados

En el lavado broncoalveolar, los ratones del grupo de ovoalbúmina presentaron un incremento significativo de leucocitos totales, con una mediana (cuartiles 25–75) de 670,0 células/ml·103 (376,2–952,5), frente a 40,0 células/ml·103 (60,0–85,0) en controles (p = 0,001), y de las fracciones eosinófila y linfocitaria en recuento diferencial. En secciones sagitales de los pulmones inflados a presión estandarizada, estos ratones mostraron hiperplasia de células caliciformes en el epitelio respiratorio —reacción de ácido peryódico de Schiff: 53,89 (36,26—62,84) frente a 0,66 (0,00–1,06) células/mm2 (p < 0,001)—, densa infiltración inflamatoria mononuclear y eosinófila —hematoxilina-eosina: 32,87 (27,34–37,13) frente a 0,06 (0,00–0,20) eosinófilos/mm2 (p = 0,002)—, infiltración subepitelial por mastocitos —azul de toluidina: 2,88 (2,00–3,28) frente a 0,28 (0,15–0,35) mastocitos/mm2 (p < 0,001)—, incremento de la masa de tejido contráctil —inmunofluorescencia para alfaactina de músculo liso: 2,60 (2,28–2,98) frente a 1,08 (0,93–1,16), adimensional (p<0,001)— e incremento del depósito de matriz extracelular (tricrómico de Masson: 2,18 (1,85–2,80) frente a 0,50 (0,37–0,65), adimensional (p < 0,001)—.

Conclusiones

Los datos aportados configuran un modelo de asma experimental inducida por exposición alergénica prolongada, con desarrollo y evaluación integrada de inflamación y remodelación de vías respiratorias.

Palabras clave:
Asma
Modelos animales de enfermedad
Inflamación
Células caliciformes
Eosinófilos
Linfocitos
Mastocitos
Músculo liso
Matriz extracelular
Full text is only aviable in PDF
References
[1.]
M. Masoli, D. Fabian, S. Holt, R. Beasley.
The global burden of asthma: executive summary of the GINA Dissemination Committee report.
[2.]
D. Ramos-Barbón.
Investigación básica en asma: ¿hacia dónde nos dirigimos?.
Arch Bronconeumol, 42 (2006), pp. 613-615
[3.]
J. Cortijo.
Modelos experimentales de asma. Aportaciones y limitaciones.
Arch Bronconeumol, 39 (2003), pp. 54-56
[4.]
D. Ramos-Barbón, M.S. Ludwig, J.G. Martin.
Airway remodeling: lessons from animal models.
Clin Rev Allergy Immunol, 27 (2004), pp. 3-22
[5.]
R. Torres, C. Picado, F. De Mora.
Descubriendo el asma de origen alérgico a través del ratón. Un repaso a la patogenia de los modelos de asma alérgica en el ratón y su similitud con el asma alérgica humana.
Arch Bronconeumol, 41 (2005), pp. 141-152
[6.]
A.L. James, J.C. Hogg, L.A. Dunn, P.D. Pare.
The use of the internal perimeter to compare airway size and to calculate smooth muscle shortening.
Am Rev Respir Dis, 138 (1988), pp. 136-139
[7.]
A.L. Lambert, D.W. Winsett, D.L. Costa, M.K. Selgrade, M.I. Gilmour.
Transfer of allergic airway responses with serum and lymphocytes from rats sensitized to dust mite.
Am J Respir Crit Care Med, 157 (1998), pp. 1991-1999
[8.]
J.R. Johnson, R.E. Wiley, R. Fattouh, F.K. Swirski, B.U. Gajewska, A.J. Coyle, et al.
Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling.
Am J Respir Crit Care Med, 169 (2004), pp. 378-385
[9.]
E.C. Cates, B.U. Gajewska, S. Goncharova, D. Álvarez, R. Fattouh, A.J. Coyle, et al.
Effect of GM-CSF on immune, inflammatory, and clinical responses to ragweed in a novel mouse model of mucosal sensitization.
J Allergy Clin Immunol, 111 (2003), pp. 1076-1086
[10.]
K.M. Murphy, A.B. Heimberger, D.Y. Loh.
Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo.
Science, 250 (1990), pp. 1720-1723
[11.]
P.G. Holt, J.E. Batty, K.J. Turner.
Inhibition of specific IgE responses in mice by pre-exposure to inhaled antigen.
Immunology, 42 (1981), pp. 409-417
[12.]
J.D. Sedgwick, P.G. Holt.
Down-regulation of immune responses to inhaled antigen: studies on the mechanism of induced suppression.
Immunology, 56 (1985), pp. 635-642
[13.]
F.K. Swirski, D. Sajic, C.S. Robbins, B.U. Gajewska, M. Jordana, M.R. Stampfli.
Chronic exposure to innocuous antigen in sensitized mice leads to suppressed airway eosinophilia that is reversed by granulocyte macrophage colony-stimulating factor.
J Immunol, 169 (2002), pp. 3499-3506
[14.]
J. Temelkovski, S.P. Hogan, D.P. Shepherd, P.S. Foster, R.K. Kumar.
An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen.
Thorax, 53 (1998), pp. 849-856
[15.]
S.J. McMillan, C.M. Lloyd.
Prolonged allergen challenge in mice leads to persistent airway remodelling.
Clin Exp Allergy, 34 (2004), pp. 497-507
[16.]
P.W. Hellings, E.M. Hessel, J.J. Van Den Oord, A. Kasran, P. Van Hecke, J.L. Ceuppens.
Eosinophilic rhinitis accompanies the development of lower airway inflammation and hyper-reactivity in sensitized mice exposed to aerosolized allergen.
Clin Exp Allergy, 31 (2001), pp. 782-790
[17.]
P.W. Hellings, J.L. Ceuppens.
Mouse models of global airway allergy: what have we learned and what should we do next?.
[18.]
C.E. Brightling, P. Bradding, F.A. Symon, S.T. Holgate, A.J. Wardlaw, I.D. Pavord.
Mast-cell infiltration of airway smooth muscle in asthma.
N Engl J Med, 346 (2002), pp. 1699-1705
[19.]
D. Ramos-Barbón, J.F. Presley, Q.A. Hamid, E.D. Fixman, J.G. Martin.
Antigen-specific CD4+ T cells drive airway smooth muscle remodeling in experimental asthma.
J Clin Invest, 115 (2005), pp. 1580-1589
[20.]
B. Herszberg, D. Ramos-Barbón, M. Tamaoka, J.G. Martin, J.P. Lavoie.
Heaves, an asthma-like equine disease, involves airway smooth muscle remodeling.
J Allergy Clin Immunol, 118 (2006), pp. 382-388
Copyright © 2009. Sociedad Española de Neumología y Cirugía Torácica
Archivos de Bronconeumología
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?