Interaction of S-protein of complement with thrombin and antithrombin III during coagulation. Protection of thrombin by S-protein from antithrombin III inactivation.
S-protein, the inhibitor in plasma of the membrane attack complex of complement, appears to have a second function in coagulation. S-protein during clotting enters into a trimolecular complex with thrombin and antithrombin III (ATIII). Functionally, S-protein in the presence of low concentrations of heparin, protects thrombin from inactivation by ATIII. Complex formation between S-protein and thrombin, and between S-protein, thrombin, and ATIII, was demonstrated by agarose gel electrophoresis and by two-dimensional immunoelectrophoresis of purified proteins and in recalcified, clotted plasma. Formation of the trimolecular S-thrombin-ATIII complex was strictly dependent on the presence of thrombin. No association was detectable between S-protein and ATIII or between S-protein and prothrombin. Heparin was not required for the formation of the bimolecular S-protein-thrombin complex or the trimolecular S-protein-ATIII complex. The protective effect of S-protein on inactivation of thrombin by ATIII was demonstrated in functional assays with purified proteins and in plasma only in the presence of low concentrations of heparin. Thus, S-protein may mediate its effect by scavenging heparin required for ATIII activation. It is suggested that the protection of thrombin by S-protein from inactivation by ATIII may be of physiological importance.
D000990:Antithrombin III / Q000378:metabolism* / Q000494:pharmacology; D001777:Blood Coagulation; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D008562:Membrane Glycoproteins; D011486:Protein C; D013917:Thrombin / Q000378:metabolism*; D019096:Vitronectin
D000990:Antithrombin III; D006023:Glycoproteins; D006493:Heparin; D008562:Membrane Glycoproteins; D011486:Protein C; D013917:Thrombin; D019096:Vitronectin