Activated platelets but not endothelial cells participate in the initiation of the consolidation phase of blood coagulation.
To address the question of whether initiation of the consolidation phase of coagulation occurs on platelets or on endothelium, we have examined the interaction of coagulation factor XI with human umbilical vein endothelial cells (HUVEC) and with platelets. In microtiter wells factor XI binds to more sites in the absence of HUVEC (1.8 x 10(10) sites/well, K(D) = 2.6 nm) than in their presence (1.3 x 10(10) sites/well, K(D) = 12 nm) when high molecular weight kininogen (HK) and zinc are present. Binding was volume-dependent and abrogated by HUVEC or Chinese hamster ovary cells and was a function of nonspecific binding of HK to the artificial plastic surface. Factor XI did not bind to HUVEC or to HEK293 cell monolayers anchored to microcarrier beads. Activation of HUVEC resulted in von Willebrand's factor secretion, but factor XI binding was not observed. Only activated platelets supported factor XI binding in the presence of HK and zinc (K(D) = 8 nm, B(max) = 1319 sites/cell). Activation of factor XI was observed in plasma in the presence of platelets activated by the thrombin receptor activation peptide but not with activated HUVEC. These results support the concept that activated platelets, but not endothelial cells, expose a procoagulant surface for binding and activating factor XI, thereby initiating the consolidation phase of coagulation.
Baird
T Regan
TR
Sol Sherry Thrombosis Research Center, Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Walsh
Peter N
PN
D000818:Animals; D001665:Binding Sites; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology*; D005172:Factor XI / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D015539:Platelet Activation; D011485:Protein Binding; D014471:Umbilical Veins / Q000166:cytology; D015032:Zinc / Q000378:metabolism
D005172:Factor XI; D015032:Zinc