Airway hyperreactivity is associated with specific leukocyte subset infiltration in a mouse model of allergic airway...

Airway hyperreactivity is defined as an increased bronchoconstrictor response to physical, pharmacological, or other stimuli. Patients with asthma develop airway hyperreactivity as well as peribronchial inflammation. We employed an established schistosome soluble egg antigen (SEA)-induced murine model of allergic inflammation to examine the temporal relationship between airway hyperreactivity and leukocyte subset infiltration. Dose response curves of intravenous methacholine were used in mice to characterize airway reactivity at various time points after intranasal SEA rechallenge. Cellular infiltration into the airspace was assessed by bronchoalveolar lavage. Airway hyperreactivity increased as early as 1 h postchallenge. Peak hyperreactivity occurred at 8 h postchallenge. Subsequently, reactivity decreased at 24 h and fell to the level observed in controls by 48 h. Neutrophil influx correlated directly with the increase in airway reactivity, as neutrophils were observed as early as 1 h, peaked at 8 h, diminished by 24 h and were not detected at 48 h post-SEA challenge. In contrast, eosinophil infiltration was not observed until 24 h and peaked at 48 h post-SEA rechallenge when increases in airway reactivity were not detected. Airway resistance induced by methacholine correlated with neutrophil (r2 = 0.90) but not eosinophil (r2 = 0.1) infiltration. These results suggest that the airway hyperreactivity observed during allergic airway inflammation correlates with airways neutrophilia and weakly eosinophil accumulation.