Development of a Murine Model of Airway Inflammation and Remodeling in Experimental Asthma

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/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 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.