HUMAN EOSINOPHIL MAJOR BASIC-PROTEIN AUGMENTS BRONCHOCONSTRICTION INDUCED BY INTRAVENOUS AGONISTS IN GUINEA-PIGS

The direct effect of intratracheal (IT) administration of human major basic protein (MBP) on pulmonary inspiratory pressure (PIP), and the e ffect on agonist-induced change in PIP, were determined in anesthetize d, ventilated-guinea pigs. 500 mug MBP increased PIP from 24.1 +/- 4.3 to 49.8 +/- 7.4 cmH2O (p < 0.002, n = 10). Maximum PIP was achieved w ithin 30 min after 500 mug MBP. The direct PIP response to 250 mug MBP was not different from vehicle. The PIP responses to intravenous (IV) acetylcholine (Ach) and 5-hydroxytryptamine (5-HT) were measured befo re and after administration of 250 mug MBP (n = 12). MBP caused a mode st, but significant potentiation of the increase in PIP induced by 1, 3 and 10 mug/kg Ach (24, 32 and 28 %, respectively, p < 0.02) and to 1 mug/kg 5-HT (43 % p < 0.02). We conclude that MBP at a dose that does not directly affect inspiratory pressure is capable of augmenting the PIP response to IV Ach and 5-HT in vivo.