Desarrollo de un modelo murino de inflamación y remodelación de vías respiratorias en asma experimental

Background and ObjectiveExperimental 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 MethodsBALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks.ResultsOn bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25–Q75) of 670.0 cells/mL×10³ (376.2, 952.5) in comparison with 40.0 cells/mL×10³ (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).ConclusionsOur 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.