Original Article
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
Rebeca Fraga-Iriso, Laura Núñez-Naveira, Nadia S. Brienza, Alberto Centeno-Cortés, Eduardo López-Peláez, Héctor Verea, David Ramos-Barbón
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Unidad de Investigación Respiratoria, Servicio de Neumología, Complejo Hospitalario Universitario, Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, Spain
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Brienza, Alberto Centeno-Cortés, Eduardo López-Peláez, Héctor Verea, David Ramos-Barbón" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Rebeca" "apellidos" => "Fraga-Iriso" ] 1 => array:2 [ "nombre" => "Laura" "apellidos" => "Núñez-Naveira" ] 2 => array:2 [ "nombre" => "Nadia S." "apellidos" => "Brienza" ] 3 => array:2 [ "nombre" => "Alberto" "apellidos" => "Centeno-Cortés" ] 4 => array:2 [ "nombre" => "Eduardo" "apellidos" => "López-Peláez" ] 5 => array:2 [ "nombre" => "Héctor" "apellidos" => "Verea" ] 6 => array:4 [ "nombre" => "David" "apellidos" => "Ramos-Barbón" "email" => array:1 [ 0 => "David.Ramos.Barbon@sergas.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Unidad de Investigación Respiratoria, Servicio de Neumología, Complejo Hospitalario Universitario, Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Desarrollo de un modelo murino de inflamación y remodelación de vías 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 => "Inflamación" 3 => "Células caliciformes" 4 => "Eosinófilos" 5 => "Linfocitos" 6 => "Mastocitos" 7 => "Músculo 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. We present a murine model of experimental asthma that allows integrated, quantitative assessment of airway inflammation and remodeling.</p> <span class="elsevierStyleSectionTitle">Material and Methods</span><p class="elsevierStyleSimplePara elsevierViewall">BALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks.</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">On bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25-Q75) of 670.0 cells/mL×10<span class="elsevierStyleSup">-3</span> (376.2-952.5) in comparison with 40.0 cells/ mL×10<span class="elsevierStyleSup">-3</span> (60.0-85.0) in controls (<span class="elsevierStyleItalic">P</span>=.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/mm<span class="elsevierStyleSup">2</span> vs 0.66 [0.00-1.06] cells/mm<span class="elsevierStyleSup">2</span>, <span class="elsevierStyleItalic">P</span><.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34-37.13] eosinophils/mm<span class="elsevierStyleSup">2</span> vs 0.06 [0.00-0.20] eosinophils/mm<span class="elsevierStyleSup">2</span>, <span class="elsevierStyleItalic">P</span>=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00-3.28] mast cells/mm<span class="elsevierStyleSup">2</span> vs 0.28 [0.15-0.35] mast cells/mm<span class="elsevierStyleSup">2</span>, <span class="elsevierStyleItalic">P</span><.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, <span class="elsevierStyleItalic">P</span><.001) and enhanced extracellular matrix deposition (Masson's trichrome, 2.18 [1.85-2.80] vs 0.50 [0.37-0.65], dimensionless, <span class="elsevierStyleItalic">P</span><.001).</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.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Introducción</span><p class="elsevierStyleSimplePara elsevierViewall">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.</p> <span class="elsevierStyleSectionTitle">Material y métodos</span><p class="elsevierStyleSimplePara elsevierViewall">Se sensibilizó a ovoalbúmina a ratones Balb/c y se les realizó broncoprovocación con ovoalbúmina o excipiente 3 veces por semana durante 12 semanas.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">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·10<span class="elsevierStyleSup">3</span> (376,2–952,5), frente a 40,0 células/ml·10<span class="elsevierStyleSup">3</span> (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/mm<span class="elsevierStyleSup">2</span> (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/mm<span class="elsevierStyleSup">2</span> (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/mm<span class="elsevierStyleSup">2</span> (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)—.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">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.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 5 | 8 |
| 2024 October | 31 | 28 | 59 |
| 2024 September | 40 | 16 | 56 |
| 2024 August | 49 | 36 | 85 |
| 2024 July | 24 | 25 | 49 |
| 2024 June | 29 | 25 | 54 |
| 2024 May | 43 | 32 | 75 |
| 2024 April | 25 | 26 | 51 |
| 2024 March | 22 | 13 | 35 |
| 2024 February | 19 | 22 | 41 |
| 2023 March | 4 | 3 | 7 |
| 2023 February | 17 | 20 | 37 |
| 2023 January | 17 | 22 | 39 |
| 2022 December | 25 | 32 | 57 |
| 2022 November | 16 | 26 | 42 |
| 2022 October | 24 | 38 | 62 |
| 2022 September | 26 | 27 | 53 |
| 2022 August | 19 | 46 | 65 |
| 2022 July | 27 | 40 | 67 |
| 2022 June | 21 | 32 | 53 |
| 2022 May | 17 | 40 | 57 |
| 2022 April | 19 | 21 | 40 |
| 2022 March | 18 | 35 | 53 |
| 2022 February | 15 | 25 | 40 |
| 2022 January | 21 | 37 | 58 |
| 2021 December | 11 | 50 | 61 |
| 2021 November | 21 | 48 | 69 |
| 2021 October | 21 | 59 | 80 |
| 2021 September | 19 | 70 | 89 |
| 2021 August | 11 | 41 | 52 |
| 2021 July | 23 | 50 | 73 |
| 2021 June | 14 | 49 | 63 |
| 2021 May | 26 | 44 | 70 |
| 2021 April | 93 | 120 | 213 |
| 2021 March | 42 | 29 | 71 |
| 2021 February | 35 | 25 | 60 |
| 2021 January | 27 | 21 | 48 |
| 2020 December | 22 | 27 | 49 |
| 2020 November | 15 | 13 | 28 |
| 2020 October | 30 | 22 | 52 |
| 2020 September | 54 | 16 | 70 |
| 2020 August | 77 | 13 | 90 |
| 2020 July | 40 | 23 | 63 |
| 2020 June | 14 | 11 | 25 |
| 2020 May | 37 | 20 | 57 |
| 2020 April | 44 | 34 | 78 |
| 2020 March | 32 | 12 | 44 |
| 2020 February | 71 | 12 | 83 |
| 2020 January | 44 | 23 | 67 |
| 2019 December | 27 | 16 | 43 |
| 2019 November | 14 | 10 | 24 |
| 2019 October | 3 | 14 | 17 |
| 2019 September | 23 | 12 | 35 |
| 2019 August | 11 | 8 | 19 |
| 2019 July | 13 | 16 | 29 |
| 2019 June | 10 | 12 | 22 |
| 2019 May | 16 | 10 | 26 |
| 2019 April | 47 | 20 | 67 |
| 2019 March | 14 | 13 | 27 |
| 2019 February | 9 | 10 | 19 |
| 2019 January | 5 | 6 | 11 |
| 2018 December | 6 | 11 | 17 |
| 2018 November | 17 | 11 | 28 |
| 2018 October | 29 | 16 | 45 |
| 2018 September | 8 | 9 | 17 |
| 2018 May | 11 | 1 | 12 |
| 2018 April | 2 | 6 | 8 |
| 2018 March | 4 | 2 | 6 |
| 2018 February | 8 | 7 | 15 |
| 2018 January | 3 | 4 | 7 |
| 2017 December | 7 | 7 | 14 |
| 2017 November | 4 | 3 | 7 |
| 2017 October | 4 | 8 | 12 |
| 2017 September | 4 | 12 | 16 |
| 2017 August | 9 | 10 | 19 |
| 2017 July | 16 | 17 | 33 |
| 2017 June | 10 | 11 | 21 |
| 2017 May | 4 | 8 | 12 |
| 2017 April | 3 | 6 | 9 |
| 2017 March | 2 | 15 | 17 |
| 2017 February | 4 | 2 | 6 |
| 2017 January | 3 | 2 | 5 |
| 2016 December | 7 | 6 | 13 |
| 2016 November | 10 | 5 | 15 |
| 2016 October | 13 | 6 | 19 |
| 2016 September | 5 | 6 | 11 |
| 2016 August | 4 | 2 | 6 |
| 2016 July | 1 | 0 | 1 |
| 2016 May | 2 | 0 | 2 |
| 2016 April | 1 | 0 | 1 |
| 2016 March | 9 | 0 | 9 |
| 2016 February | 4 | 0 | 4 |
| 2016 January | 6 | 0 | 6 |
| 2015 December | 3 | 0 | 3 |
| 2015 October | 46 | 17 | 63 |
| 2015 September | 47 | 6 | 53 |
| 2015 August | 40 | 11 | 51 |
| 2015 July | 60 | 7 | 67 |
| 2015 June | 37 | 8 | 45 |
| 2015 May | 49 | 17 | 66 |
| 2015 April | 40 | 10 | 50 |
| 2015 March | 35 | 5 | 40 |
| 2015 February | 45 | 7 | 52 |
| 2015 January | 36 | 7 | 43 |
| 2014 December | 30 | 6 | 36 |
| 2014 November | 54 | 6 | 60 |
| 2014 October | 41 | 9 | 50 |
| 2014 September | 43 | 11 | 54 |
| 2014 August | 38 | 9 | 47 |
| 2014 July | 46 | 7 | 53 |
| 2014 June | 53 | 9 | 62 |
| 2014 May | 59 | 7 | 66 |
| 2014 April | 64 | 6 | 70 |
| 2014 March | 65 | 9 | 74 |
| 2014 February | 73 | 9 | 82 |
| 2014 January | 59 | 10 | 69 |
| 2013 December | 56 | 9 | 65 |
| 2013 November | 48 | 5 | 53 |
| 2013 October | 49 | 9 | 58 |
| 2013 September | 56 | 13 | 69 |
| 2013 August | 44 | 4 | 48 |
| 2013 July | 49 | 11 | 60 |
| 2013 June | 39 | 7 | 46 |
| 2013 May | 26 | 8 | 34 |
| 2013 April | 15 | 5 | 20 |
| 2013 March | 6 | 2 | 8 |
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