title: The activation of human blood coagulation factor X on the surface of endothelial cells: a comparison with various vascular cells, platelets and monocytes.
abstract: Rates of factor X activation on endothelial cells were compared with activation rates on other vascular cells, platelets, monocytes and negatively charged phospholipid vesicles. Factor VIIa-mediated factor X activation was observed on smooth muscle cells and fibroblasts in the absence of cell-perturbing agents, whereas endothelial cells required activation in order to allow extrinsic activation of factor X. On the other hand, unperturbed endothelial cells did promote intrinsic, factor VIII/IXa-dependent activation of factor X. The rate of factor X activation on these cells was about one-sixth of that on ionophore A23187-stimulated platelets. Also, smooth muscle cells and fibroblasts were able to activate factor X through the intrinsic pathway, although to a lesser 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 vitamin K-dependent coagulation factors to phospholipid surfaces, inhibited factor VIII/IXa-dependent factor X activation on endothelial cells (IC50 3.2 microM) to a lesser extent than on phospholipid vesicles (IC50 0.2 microM). 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 without effect on intrinsic activation of factor X. This observation indicates that membrane constituents of endothelial cells involved in factor VIII/IXa-dependent activation of factor X are constitutively expressed.
authors.affiliation: Department of Blood Coagulation, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: H J
authors.initials: HJ
authors.lastname: Brinkman
authors.forename: K
authors.initials: K
authors.lastname: Mertens
authors.forename: J
authors.initials: J
authors.lastname: Holthuis
authors.forename: L A
authors.initials: LA
authors.lastname: Zwart-Huinink
authors.forename: K
authors.initials: K
authors.lastname: Grijm
authors.forename: J A
authors.initials: JA
authors.lastname: van Mourik
mesh_terms: D001777:Blood Coagulation / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism*; D001808:Blood Vessels / Q000166:cytology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D015949:Factor IXa / Q000494:pharmacology; D005169:Factor VIII / Q000494:pharmacology; D015942:Factor VIIa / Q000494:pharmacology; D005170:Factor X / Q000187:drug effects / Q000378:metabolism*; D015951:Factor Xa / Q000096:biosynthesis; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000378:metabolism*
chemical_list: D005169:Factor VIII; D005170:Factor X; D015942:Factor VIIa; D015949:Factor IXa; D015951:Factor Xa