EFFECT OF FORMOTEROL ON SUPEROXIDE ANION GENERATION FROM BRONCHOALVEOLAR LAVAGE CELLS AFTER ANTIGEN CHALLENGE IN GUINEA-PIGS

It is well known that antigen challenge of sensitized subjects can induce an immediate and late asthmatic response, airway eosinophilia, and hyperreactivity. Using our modified guinea pig asthma model, we investigated the superoxide anion generation from eosinophils and macrophages recovered from bronchoalveolar lavage (BAL) 24 h after antigen (ovalbumin) challenge. We also investigated the effect of formoterol, a new long-acting selective beta2-agonist, on these functions. Antigen challenge increased the total cell counts and the ratio of eosinophils in BAL. Eosinophils and macrophages were collected using discontinuous density centrifugation. Antigen challenge enhanced superoxide anion generation from eosinophils, from 5.39 +/- 1.08 to 13.19 +/- 1.95 nmol 60 min after phorbol myristate acetate (PMA) (1 ng/ml) activation, and 0.22 +/- 0.49 to 3.34 +/- 1.67 nmol 40 min after platelet-activating factor (PAF) (10(-6) M) activation. Formoterol treatment before antigen challenge prevented these enhancements. Superoxide anion generation from macrophages was also enhanced by antigen challenge, from 6.57 +/- 0.76 to 10.66 +/- 0.88 nmol 60 min after PMA activation, and 4.20 +/- 1.17 to 6.63 +/- 0.64 nmol 60 min after PAF activation. Formoterol, however, failed to inhibit enhancement of superoxide anion generation from macrophages. These results show antigen challenge of sensitized guinea pigs induces an increase of eosinophils and macrophages in BAL and enhances the functional characteristics of both cells. Formoterol had inhibitory effects on the enhancement of superoxide anion generation from eosinophils but did not have this effect on macrophages.