[Development of a murine model of airway inflammation and remodeling in experimental asthma].
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.


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 x 10(3) (376.2, 952.5) in comparison with 40.0 cells/mL x 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/mm(2) vs 0.66 [0.00-1.06]cells/mm(2), P<.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34-37.13]eosinophils/mm(2) vs 0.06 [0.00-0.20]eosinophils/mm(2), P=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00-3.28] mast cells/mm(2) vs 0.28 [0.15-0.35] mast cells/mm(2), P<.001), increased contractile tissue mass (immunofluorescence analysis for alpha-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.
Fraga-Iriso
Rebeca
R
Unidad de Investigación Respiratoria, Servicio de Neumología, Complejo Hospitalario Universitario, Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, España.
Núñez-Naveira
Laura
L
Brienza
Nadia S
NS
Centeno-Cortés
Alberto
A
López-Peláez
Eduardo
E
Verea
Héctor
H
Ramos-Barbón
David
D
D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007114:Immunization / Q000379:methods; D007249:Inflammation; D008168:Lung / Q000473:pathology; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D012137:Respiratory System / Q000382:microbiology / Q000473:pathology; D013194:Staining and Labeling / Q000379:methods; D018418:Th2 Cells / Q000276:immunology
D010047:Ovalbumin