ENGAGEMENT OF HUMAN PECAM-1 (CD31) ON HUMAN ENDOTHELIAL-CELLS INCREASES INTRACELLULAR CALCIUM-ION CONCENTRATION AND STIMULATES PROSTACYCLINRELEASE

Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is a member of the immunoglobulin superfamily that plays a role in a number of endot helial cell (EC) functions including migration, angiogenesis, and tran smigration of leukocytes across endothelium. We postulated that one wa y PECAM-1 might exert its effects was by regulating intracellular EC l evels of calcium, Using single-cell fluorometry, we found that engagem ent of PECAM-1 by mAbs induced a slow but sustained increase in intrac ellular calcium, both in EC and in an adherent PECAM-1-transfected cel l line that models endothelium. Generation of this signal was specific for certain anti-PECAM-1 antibodies, required the presence of the cyt oplasmic domain, depended on extracellular calcium and on tyrosine pho sphorylation, but did not require crosslinking; in fact, calcium incre ases were stimulated by certain Fab fragments, Activation of EC by PEC AM-1 also caused a time-dependent increase in prostacyclin release, Gi ven the importance of intracellular calcium and prostacyclin release a s signaling molecules, engagement of PECAM-1 during cell-cell interact ions may alter a number of EC functions including secretion of vasoact ive mediators.