P-SELECTIN INDUCES THE EXPRESSION OF TISSUE FACTOR ON MONOCYTES

P selectin on activated platelets and stimu lated endothelial cells me diates cell adhesion with monocytes and neutrophils. Since activated p latelets induce tissue factor on mononuclear leukocytes, we examined t he effect of P-selectin on the expression of tissue factor activity in monocytes. Purified P-selectin stimulated tissue factor expression on mononuclear leukocytes in a dose dependent manner. Chinese hamster ov ary (CHO) cells expressing P-selectin stimulated tissue factor procoag ulant activity in purified monocytes, whereas untransfected CHO cells and CHO cells expressing E-selectin did not. Anti-P-selectin antibodie s inhibited the effects of purified P-selectin and CHO cells expressin g P-selectin on monocytes. Incubation of CHO cells expressing P-select in with monocytes leads to the development of tissue factor mRNA in mo nocytes and to the expression of tissue factor antigen on the monocyte surface. These results indicate that P-selectin upregulates the expre ssion of tissue factor on monocytes as well as mediates the binding of platelets and endothelial cells with monocytes and neutrophils. The b inding of P selectin to monocytes in the area of vascular injury may b e a component of a mechanism that initiates thrombosis.