Activated platelets induce tissue factor expression on human umbilical vein endothelial cells by ligation of CD40

CD40 is a type I member of the tumour necrosis factor (TNF) receptor superf amily of proteins, and is present on a wide variety of cells including vasc ular endothelial cells. Ligation of this receptor on endothelial cells is k nown to increase expression of inflammatory adhesion molecules. We have rec ently demonstrated that platelets express the ligand of CD40 (CD154) within seconds of exposure to agonist, and interact with endothelial cells to par ticipate directly in the induction of an inflammatory response. Here we sho w that activated platelets induce tissue factor (TF) expression on endothel ial cells in a CD40/CD 154-dependent manner, and that the magnitude of this response can equal that induced by TNF alpha. Moreover, CD40 ligation on e ndothelial cells downregulates the expression of thrombomodulin. We also sh ow that CD40-mediated TF expression is less sensitive to inhibition with th e oxidative radical scavenger pyrrolidine dithiocarbamate than is that medi ated by TNF alpha, indicating that CD40 has a distinct signalling pathway. Tissue factor is a cell membrane protein which functions as the main trigge r of the extrinsic pathway of blood coagulation, and its expression on endo thelial cells is implicated in wound healing and angiogenesis. Since platel ets are among the first cells involved in haemostasis following tissue inju ry, our data showing that ligation of CD40 by CD154 induces a procoagulant phenotype on vascular endothelial cells suggests that platelets may play an important role in the induction of wound healing.