Pulmonary eosinophilia correlates with allergen deposition to the lower respiratory tract in a mouse model of asthma

Abstract

Eosinophilic infiltration into the airways is frequently associated with allergic asthma; however, the role of antigen deposition in mediating this phenomenon has not been studied in detail. Using a murine model of ovalbumin (OVA) allergy, we examined how differential deposition of OVA during antigen challenge affects pulmonary eosinophilia, immune response and airway hyper-reactivity (AHR). Differential allergen deposition to the upper respiratory tract (URT) alone or combined upper and lower respiratory tract (ULRT) was accomplished by administering OVA intranasally to either anaesthetized or unanaesthetized mice, respectively. BALB/c mice (6-7 weeks old) were sensitized with OVA-alum via the intraperitoneal route, and then challenged intranasally using OVA, with or without anaesthesia. AHR, enumeration of inflammatory cells and quantitative measurement of inflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF), lung histopathology and immune responses were subsequently assessed. In sensitized animals challenged via the ULRT route, a profound eosinophilia and goblet cell hyperplasia was observed in lung tissue. Conversely, sensitized mice receiving an identical challenge dose via the URT route alone exhibited only negligible levels of inflammation. Interestingly, AHR and OVA-specific IgG(1) and IgE systemic responses were comparable between the two groups. This study indicates that direct exposure of allergen in the deep lung is highly correlated with airway eosinophilia and lung inflammation, but does not correlate with AHR or immune response.