ROLE OF EOSINOPHIL ACTIVATION IN THE BRONCHIAL REACTIVITY OF ALLERGIC GUINEA-PIGS

Ovalbumin inhalation by sensitized guinea pigs induced a marked increase in the number of eosinophils (0.89 +/- 0.18 to 5.45 +/- 0.77 x 10(5)/ml, n = 10, p < 0.05) and elevations in the amounts of protein and eosinophil-derived major basic protein (MBP) (1,010.7 +/- 184.9 to 4,116.6 +/- 973.0 ng/ml, n = 10, p < 0.05) recovered by bronchoalveolar lavage (BAL). in contrast, no changes in the levels of eosinophil peroxidase (EPO) or in the sensitivity of the airways to bronchoconstriction induced by methacholine were detected. However, when ovalbumin-exposed guinea pigs received an intratracheal instillation of 1 mu g leukotriene (LT)B-4 30 min prior to methacholine provocation, elevated levels of EPO and MBP in the BAL fluid and a marked bronchial hyperreactivity to methacholine were noted when compared with saline-challenged LTB(4)-injected animals (p < 0.05). In contrast, the intratracheal instillation of 1 or 3 mu g platelet-activating factor (PAF) did not significantly modify the bronchial reactivity to methacholine or the levels of EPO and MBP. PAF and LTB(4) induced similar enhancements in the amount of protein in BAL fluids from antigen-exposed guinea pigs, suggesting that increased endothelial/epithelial permeability does not account for bronchial hyperreactivity. A significant correlation between the levels of EPO or MBP and the intensity of the bronchial responsiveness to methacholine were shown in ovalbumin-challenged guinea pigs, irrespective of their subsequent treatment, i.e., either with PAF or with LTB(4) or with their vehicle (r = 0.579, p = 0.0002 and r = 0.330, p = 0.049, n 36 for EPO and MBP, respectively), These results indicate that eosinophil activation rather than accumulation per se is required for the development of bronchial hyperreactivity in the guinea pig.