Kinetics of inflammation and leukocyte recruitment in a murine model of asthma: eosinophils versus neutrophils (HYP7P.284)

Abstract

Abstract Murine model of ovalbumin-induced allergic inflammation remains to be a popular choice for approximating human acute asthma condition. Despite its widespread usage, exact timing and sequence of inflammatory events in this model remain obscure. We used a BALB/cJ mouse model with two intraperitoneal sensitizations and six intranasal challenges, and monitored inflammatory parameters at 6 and 24 hours after each ovalbumin challenge. Multicolor flow cytometry was used to assess recruitment dynamics of leukocytes in the digested lung tissue and bronchoalveolar lavage (BAL). Although neutrophil recruitment dominated the initial response to allergen, eosinophils started to appear almost simultaneously, gradually increasing their presence with each challenge. Interestingly, while still present in the lung tissue, neutrophils ceased mucosal surveillance (measured as BAL infiltrate) after three challenges, at which time point eosinophilia increased dramatically. This increase in BAL eosinophilia correlated with upregulation of integrin CD11c by CD11b+Siglec-F+Ly6Glow eosinophils in the tissue. Mediators such as IL-4, IL-6, IL-9 and IL-33 exhibited peak expression during the first three challenges. Other mediators, such as CCL11, IL-5, IL-13 and Slit2-roundabout signals were more prevalent later in the model. Collectively, our results demonstrate progression of events that govern presence of eosinophils versus neutrophils in the lung tissue and airways during allergic inflammation.