THE VITRONECTIN RECEPTOR (ALPHA(V),BETA(3)) IS IMPLICATED, IN COOPERATION WITH P-SELECTIN AND PLATELET-ACTIVATING-FACTOR, IN THE ADHESION OF MONOCYTES TO ACTIVATED ENDOTHELIAL-CELLS

In this study we have investigated the presence on endothelial cells of potential glycoprotein receptors, other than beta-selectin, which are involved in the adhesion of monocytes at the early stages of activation. We report that the majority of cells binding to thrombin-activated endothelial cells from a peripheral blood mononuclear cell (PBMC) preparation are monocytes. The adhesion of PBMC to thrombin-activated, but not resting, endothelial cells was inhibited (66%) by a monoclonal antibody (mAb) directed against alpha(v) beta(3). Elutriated monocytes or a monocytic cell line (U937) were also inhibited by this antibody, its F(ab)'(2) fragments and three other anti-(alpha(v) beta(3)) mAbs. alpha(v) beta(3) isolated from endothelial-cell lysates significantly inhibited the adhesion of monocytes and U937 cells to endothelial cells. A peptide motif (RGDF) known to interact with alpha(v) beta(3) inhibited U937 cell adhesion to activated endothelial cells by 53%. Finally, an anti-(P-selectin) mAb (LYP20) or a platelet-activating factor (PAF)-receptor antagonist (WEB 2086) inhibited monocyte adhesion to activated endothelial cells. This study shows for the first time that alpha(v) beta(3) is implicated, in addition to P-selectin and PAF, in the adhesion of monocytes to activated endothelial cells.