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 effect on agonist-induced change in PIP, were determined in anesthetized, 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 within 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 before and after administration of 250 mug MBP (n = 12). MBP caused a modest, 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.