TRIPLE ROLE OF PLATELET-ACTIVATING-FACTOR IN EOSINOPHIL MIGRATION ACROSS MONOLAYERS OF LUNG EPITHELIAL-CELLS - EOSINOPHIL CHEMOATTRACTANT AND PRIMING AGENT AND EPITHELIAL-CELL ACTIVATOR

Infiltration of eosinophils into the lung lumen is a hallmark of aller gic asthmatic inflammation. To reach the lung lumen, eosinophils must migrate across the vascular endothelium, through the interstitial matr ix, and across the lung epithelium. The regulation of this process is obscure. In this study, we investigated the migration of human eosinop hils across confluent monolayers of either human lung H292 epithelial cells or primary human bronchial epithelial cells. Established eosinop hil chemoattractants (IL-8, RANTES, platelet-activating factor (PAF), leukotriene B-4, and complement fragment 5a (C5a)) or activation of th e epithelial cells with IL-1 beta induced little eosinophil transmigra tion (<7% in 2 h), In contrast, addition of PAP in combination with C5 a induced extensive (>20%) transepithelial migration of unprimed and I L-5-primed eosinophils Eosinophil migration assessed in a Boyden chamb er assay, i.e., without an epithelial monolayer, was only slightly inc reased upon addition of PAF and C5a, Preincubation of eosinophils with the PAF receptor antagonist WEB 2086 only inhibited migration of unpr imed eosinophils toward PAF and C5a, whereas preincubation of epitheli al cells with WEB 2086 abolished migration of both IL-5-primed and unp rimed eosinophils, This latter result indicated the presence of PAF re ceptors on epithelial cells. Indeed, addition of PBF to epithelial cel ls induced an increase in cytosolic free Ca2+, which was blocked by th e PAF receptor antagonists WEB 2086 and TCV-309, Our results show that PAF induces permissive changes in epithelial cells, and that PAI: act s as a chemoattractant and priming agent for the eosinophils.