Augmentation of eosinophil degranulation and LTC4 secretion by integrin-mediated endothelial cell adhesion

We examined the effect of eosinophil ligation to cultured human umbilical v ein endothelial cells (HUVECs) in augmenting the stimulated secretion of le ukotriene (LT) C-4 and eosinophil peroxidase (EPO). The effects of adhesion were compared before and after specific blockade with monoclonal antibodie s directed against eosinophil surface integrins or endothelial counterligan ds. Adhesion to HUVECs augmented EPO release caused by formyl-methionyl-leu cyl-phenylalanine plus cytochalasin B from 403 +/- 15.3 (BSA control) to 77 8 +/- 225 ng/10(6) cells for eosinophils exposed to interleukin-1 alpha-tre ated HUVECs (P < 0.05) and also caused a twofold increase in stimulated LTC 4 secretion (P < 0.05). To determine whether augmented secretion resulted d irectly from adhesive ligation, studies were also performed with paraformal dehyde-treated HUVECs; stimulated secretion of LTC4 from eosinophils was co mparable to that for living HUVECs. Our study is the first demonstration th at adhesion to HUVECs through ligation to alpha(4)- or beta(2)-integrin on the eosinophil surface causes augmentation of stimulated secretion of both EPO and LTC4 and that blockade of adhesion molecules on either eosinophils or HUVECs prevents the priming effect on eosinophil secretion.