COMPLEMENT-MEDIATED REGULATION OF TISSUE FACTOR ACTIVITY IN ENDOTHELIUM

Inflammation and immunity may be associated with endothelial cell (EC) injury and thrombus formation. We explored the mechanisms through whi ch a humoral immune response directed against the endothelium might pr omote coagulation. Using the interaction of anti-EC antibodies and com plement (C) with cultured EC as a model, we studied the expression and function of tissue factor, a cofactor for factor VIIa-mediated conver sion of factor X to Xa. Exposure of EC to anti-EC antibodies and C in sublytic amounts stimulated the synthesis of tissue factor over a peri od of 16-42 h. Cell surface expression of tissue factor activity requi red activation of C and assembly of the membrane attack complex, becau se expression was inhibited by soluble CR1 and was not detected in the absence of C8. Elaboration of tissue factor messenger RNA was observe d over a period of 8-30 h and required protein synthesis. Expression o f tissue factor was not a direct consequence of the action of C on the EC but was a secondary response that required as an intermediate step the release of interleukin 1 alpha, an early product of the EC respon se to C activation. These findings suggest that, after the assembly of membrane attack complex on EC, the production of tissue factor and in itiation of coagulation in a blood vessel depend on the production of interleukin 1 alpha and on its availability to stimulate affected EC.