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 ind uce an immediate and late asthmatic response, airway eosinophilia, and hyperreactivity. Using our modified guinea pig asthma model, we inves tigated the superoxide anion generation from eosinophils and macrophag es recovered from bronchoalveolar lavage (BAL) 24 h after antigen (ova lbumin) challenge. We also investigated the effect of formoterol, a ne w long-acting selective beta2-agonist, on these functions. Antigen cha llenge increased the total cell counts and the ratio of eosinophils in BAL. Eosinophils and macrophages were collected using discontinuous d ensity centrifugation. Antigen challenge enhanced superoxide anion gen eration 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 fa ctor (PAF) (10(-6) M) activation. Formoterol treatment before antigen challenge prevented these enhancements. Superoxide anion generation fr om 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, how ever, failed to inhibit enhancement of superoxide anion generation fro m macrophages. These results show antigen challenge of sensitized guin ea 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 f rom eosinophils but did not have this effect on macrophages.