Inhibition of the Thrombin-Fibrinogen Reaction by α₂-Macroglobulin, Studied by N-Terminal Analysis

Summary

The influence of α₂-macroglobulin on the thrombin-fibrinogen reaction was studied with purified human reagents. The N-terminal changes reflecting fibrinopeptide release was measured.

α₂-macroglobulin inhibited progressively the release of fibrinopeptides A and B. Fibrin polymerization was not influenced. The amount of fibrin formed depended on thrombin and α₂-macroglobulin concentrations. When initial thrombin concentration was below 0.2 NIH units/ml, physiological α₂-macroglobulin concentrations reduced fibrin formation. The contribution of α₂-macroglobulin to the inhibition of the thrombin-fibrinogen reaction in plasma was evaluated.

• References

• 1 Steinbuch M, Blatrix C, Josso F. L. L’ α₂-macroglobuline comme anti-thrombine progressive. Proc. Xlth Congr. Int. Soc. Haemat. (Sidney). 07. 1966.
• 2 Lanchantin G. F, Plesset M. L, Friedmann J. A, Hart D. W. Dissociation of esterolytic and clotting activities of thrombin by trypsin-binding macroglobulin. Proc. Soc. exp. Biol. (N. Y) 121: 444 1966;
• 3 Abildgaard U. Purification of two progressive antithrombins of human plasma. Scand. J. clin. Lab. Invest 19: 190 1967;
• 4 Abildgaard U, Egeberg O. Thrombin inhibitory activity of fractions obtained by gel filtration of antithrombin III deficient plasma. Scand. J. Haematol 05: 155 1968;
• 5 Hensen A, Loeliger E. A. Antithrombin III. Its metabolism and its function in blood coagulation. Thrombos. Diathes. haemorrh. (Stuttg) 09 Suppl. 1 1963;
• 6 Abildgaard, UN-terminal analysis during coagulation of purified human fibrinogen, fraction I, and plasma. Scand. J. clin. Lab. Invest 17: 529 1965;
• 7 Abildgaard U. Inhibition of the thrombin-fibrinogen reaction by antithrombin III, studied by N-terminal analysis. Scand. J. clin. Lab. Invest 20: 207 1967;
• 8 Edman P. Preparation of thiohydantoins from natural amino acids. Acta chem. scand 04: 277 1950;
• 9 Blombäck B, Yamashina I. On the N-terminal amino acids in fibrinogen and fibrin. Arkiv for Kemi 12: 299 1958;
• 10 Steinbuch M, Quentin M, Pejaudir L. Specific technique for the isolation of human α₂-macroglobulin. Nature (Lond) 205: 1227 1965;
• 11 Laurell G. B. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal. Biochem 15: 45 1966;
• 12 Mancini G, Vaerman J. P, Garbonara A. O, Heremans J. F. A single-radial-diffusion method for the immunological quantitation of proteins, p. 370 in Protides of the Biological Fluids, vol. 11, Proc. 11th Colloquium. Elsevier, Amsterd am. London, New York: 1964
• 13 Schultze H. E, Heremans J. F. Molecular biology of human proteins. Vol. 1. Elsevier, Amsterdam; London, New York: 1966
• 14 Berg W, Korsan-Bengtsen K, Ygge J. Human and bovine plasminogenfree thrombin, purified by means of gel filtration and ion exchange chromatography. Thrombos. Diathes. haemorrh. (Stuttg) 15: 501 1966;
• 15 Blombäck B. Studies on the action of thrombic enzymes on bovine fibrinogen as measured by N-terminal analysis. Arkiv for Kemi 12: 321 1958;
• 16 Schultze H. E, Schwick G. Quantitative immunologische Bestimmung von Plasmaproteinen. Clin. chim. Acta 04: 15 1959;
• 17 Ganrot P. O. Serum α₂-macroglobulin concentration and its variation with age and sex. Clin, chim. Acta 15: 113 1967;
• 18 Webb J. L. Enzyme and metabolic inhibitors. Vol. 1. Academic press; New York: 1963
• 19 Abildgaard U. To be published.
• 20 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thrombos. Diathes. haemorrh. (Stuttg) IS: 516 1965;
• 21 Niléhn J. E, Ganrot P. O. Plasmin, plasmin inhibitors and degradation products of fibrinogen in human serum after intravenous infusion of streptokinase. Scand. J. clin. Lab. Invest 20: 113 1967;