PECAM-1 (CD31) expression modulates bleeding time in vivo

PECAM-1 is a 130-kd member of the Ig superfamily present on endothelial cel ls, platelets, polymorphonuclear leukocytes, monocytes, and lymphocytes, It s expression begins early in development and persists through adulthood. PE CAM-1 functions as an adhesion and signaling molecule between adjacent endo thelial cells and between endothelial cells and circulating blood elements. Antibodies directed against PECAM-1 have been shown to affect angiogenesis , endothelial cell migration, and polymorphonuclear leukocyte transmigratio n Furthermore, its dimerization is associated with the modulation of Integr in affinity. Antibody inhibition studies suggest that PECAM-1 plays a role in modulating thrombosis; however, recent in vitro aggregation studies perf ormed on platelets harvested from PECAM-1-deficient mice revealed no abnorm alities. In this report we demonstrate prolonged in vivo bleeding times in PECAM-1-deficient mice. This abnormality was not corrected when wild-type h ematopoietic precursors were engrafted into marrow-ablated PECAM-1-deficien t mice. Furthermore, normal bleeding times were observed when marrow-ablate d wild-type mice were engrafted with hematopoietic precursors harvested fro m PECAM-1-deficient mice. These studies are consistent with a role for PECA M-1 in modulating thrombosis in the vasculature, which is potentially media ted by endothelial cell PECAM-1 expression.