Inhibition of factor Xa suppresses the expression of tissue factor in human monocytes and lipopolysaccharide-induced endotoxemia in rats

Background. Activated factor X (FXa) is involved in hemostasis, thrombogene sis, inflammation, and cellular immune response. Tissue factor (TF) is an i nitiator of blood coagulation. We investigated whether, FXa induces TF expr ession in human peripheral monocytes and whether treatment with FXa inhibit or reduces TF expression in an experimental model of rat endotoxemia. Methods. Human peripheral mononuclear cells were used to determine TF expre ssion induced by FXa. Experimental rat endotoxemia was induced by intraveno us bolus injection of lipopolysaccharide (LPS). A specific FXa inhibitor, D X-9065a, was administered subcutaneously immediately after LPS injection. Results. FXa induced TF expression in monocytes without intervention of thr ombin and the expression was suppressed by FXa inhibitor. In the experiment al model of rat endotoxemia, TF and TF mRNA expression levels in the liver were reduced by DX-9065a. Moreover, administration of DX-9065a suppressed t he rise in plasma concentrations of thrombin-antithrombin III complex (TAT) and monocyte chemoattractant protein-1 (MCP-1). Conclusions. Our results indicated that FXa can induce TF expression in hum an peripheral monocytes and that inhibition of FXa, reduces TF expression i n the liver of rat endotoxemia. These results suggest that FXa is an import ant factor for TF expression in sepsis.