BRONCHOCONSTRICTION AND AIRWAY HYPERRESPONSIVENESS AFTER OVALBUMIN INHALATION IN SENSITIZED MICE

To investigate the mechanisms underlying airway hyperresponsiveness a murine model was developed with several important characteristics of h uman allergic asthma, Mice were intraperitoneally sensitized with oval bumin and after 4 weeks challenged via an ovalbumin aerosol. After aer osol, lung function was evaluated with a non-invasive forced oscillati on technique. The amount of mucosal exudation into the airway lumen an d the presence of mast cell degranulation was determined. Tracheal res ponsiveness was measured at several time points after challenge. At th ese time points also bronchoalveolar lavage and histology were perform ed. Sensitization induced high antigen-specific IgE levels in serum. I nhalation of ovalbumin in sensitized mice induced an immediate but no late bronchoconstrictive response. During this immediate phase, respir atory resistance was increased (54%). Within the first hour after oval bumin inhalation increased mucosal exudation and mast cell degranulati on were observed. At 12 and 24 h after ovalbumin challenge, mice showe d tracheal hyperresponsiveness (29% and 34%, respectively). However, n o apparent inflammation was found in the lungs or bronchoalveolar lava ge. From these results it can be concluded that hyperresponsiveness ca n develop via mechanisms independent of an inflammatory infiltrate. Si nce mast cell degranulation occurred after ovalbumin exposure, we hypo thesize that mast cells are involved in the induction of airway hyperr esponsiveness in this model.