THE ACTIVATION OF HUMAN BLOOD-COAGULATION FACTOR-X ON THE SURFACE OF ENDOTHELIAL-CELLS - A COMPARISON WITH VARIOUS VASCULAR CELLS, PLATELETS AND MONOCYTES

Rates of factor X activation on endothelial cells were compared with a ctivation rates on other vascular cells, platelets, monocytes and nega tively charged phospholipid vesicles. Factor VIIa-mediated factor X ac tivation was observed on smooth muscle cells and fibroblasts in the ab sence of cell-perturbing agents, whereas endothelial cells required ac tivation in order to allow extrinsic activation of factor X. On the ot her hand, unperturbed endothelial cells did promote intrinsic, factor VIII/IXa-dependent activation of factor X. The rate of factor X activa tion on these cells was about one-sixth of that on ionophore A23187-st imulated platelets. Also, smooth muscle cells and fibroblasts were abl e to activate factor X through the intrinsic pathway, although to a le sser extent than endothelial cells. Monocytes were ineffective in this respect. Prothrombin fragment 1, the prothrombin fragment containing the gamma-carboxyglutamic acid domain known to mediate binding of vita min K-dependent coagulation factors to phospholipid surfaces, inhibite d factor VIII/IXa-dependent factor X activation on endothelial cells ( IC50 3.2 mu M) to a lesser extent than on phospholipid vesicles (IC50 0.2 mu M). Therefore, besides negatively charged phospholipids, other membrane constituents seem to be involved in endothelial cell mediated , intrinsic activation of factor X. Perturbation of endothelial cells with phorbol myristate acetate (PMA) or lipopolysaccharide (LPS) was w ithout effect on intrinsic activation of factor X. This observation in dicates that membrane constituents of endothelial cells involved in fa ctor VIII/IXa-dependent activation of factor X are constitutively expr essed.