THE IMPORTANCE OF EOSINOPHIL ACTIVATION FOR THE DEVELOPMENT OF ALLERGEN-INDUCED BRONCHIAL HYPERREACTIVITY IN CONSCIOUS, UNRESTRAINED GUINEA-PIGS

Using a newly developed guinea-pig model of asthma, characterized by allergen-induced early and late phase asthmatic reactions, bronchial hyperreactivity (BHR) and airway inflammation, the importance of eosinophil activation for the development of BHR to inhaled histamine was investigated at 6 h (after the early reaction) and 24 h (after the late reaction) after allergen provocation. Eosinophil activation was assessed by a sensitive kinetic assay for eosinophil peroxidase (EPO) activity, suitable for bronchoalveolar lavage (BAL) analysis. A significant 2.9-fold (P <0.01) increase in bronchial reactivity to histamine was observed at 6 h after allergen exposure, which was associated with a 2.9-fold increase in the number of eosinophils (P <0.05) and a 6.7-fold increase in EPO activity (P <0.01) in the BAL fluid. At 24 h after allergen exposure the bronchial reactivity to histamine was lower (1.7-fold), but still significantly enhanced (P <0.01). By contrast, the number of eosinophils was further increased compared with 6h after provocation (3.8-fold, P <0.05), while the EPO activity remained stable at 6h levels. The number of eosinophils was significantly correlated with EPO activity at 6 h (r = 0.62; P <0.05), but not at 24 h after provocation. No significant correlation was observed between the number of eosinophils in the BAL fluid and BHR to histamine at either time point. Remarkably, EPO activity was significantly correlated to BHR at 24h (r = 0.66; P