Augmentation of Eosinophil Degranulation and LTC(4) Secretion by Integrin-mediated Endothelial Cell Adhesion

We examined the effect of eosinophil ligation to cultured human umbilical vein endothelial cells (HUVECs) in augmenting the stimulated secretion of leukotriene (LT) C(4) and eosinophil peroxidase (EPO). The effects of adhesion were compared before and after specific blockade with monoclonal antibodies directed against eosinophil surface integrins or endothelial counterligands. Adhesion to HUVECs augmented EPO release caused by formyl-methionyl-leucyl-phenylalanine plus cytochalasin B from 403 +/- 15.3 (BSA control) to 778 +/- 225 ng/10(6) cells for eosinophils exposed to interleukin-1alpha-treated HUVECs (P < 0.05) and also caused a twofold increase in stimulated LTC(4) secretion (P < 0.05). To determine whether augmented secretion resulted directly from adhesive ligation, studies were also performed with paraformaldehyde-treated HUVECs; stimulated secretion of LTC(4) from eosinophils was comparable to that for living HUVECs. Our study is the first demonstration that 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 LTC(4) and that blockade of adhesion molecules on either eosinophils or HUVECs prevents the priming effect on eosinophil secretion.