Abstract
PECAM-1 is a 130-kd member of the Ig superfamily present on endothelial cells, platelets, polymorphonuclear leukocytes, monocytes, and lymphocytes. Its expression begins early in development and persists through adulthood. PECAM-1 functions as an adhesion and signaling molecule between adjacent endothelial 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 transmigration. Furthermore, its dimerization is associated with the modulation of integrin affinity. Antibody inhibition studies suggest that PECAM-1 plays a role in modulating thrombosis; however, recent in vitro aggregation studies performed on platelets harvested from PECAM-1-deficient mice revealed no abnormalities. In this report we demonstrate prolonged in vivo bleeding times in PECAM-1-deficient mice. This abnormality was not corrected when wild-type hematopoietic precursors were engrafted into marrow-ablated PECAM-1-deficient mice. Furthermore, normal bleeding times were observed when marrow-ablated wild-type mice were engrafted with hematopoietic precursors harvested from PECAM-1-deficient mice. These studies are consistent with a role for PECAM-1 in modulating thrombosis in the vasculature, which is potentially mediated by endothelial cell PECAM-1 expression.