Thrombosis and Haemostasis, Table of Contents Thromb Haemost 1982; 48(02): 208-210DOI: 10.1055/s-0038-1657258 Original Article Schattauer GmbH Stuttgart A Unique Pathway for the Plasma Elimination of α2-Antiplasmin-Protease Complexes in Mice Authors Author Affiliations S L Gonias The Departments of Pathology and Biochemistry, Duke University Medical Center, Durham, North Carolina, U.S.A. H E Fuchs The Departments of Pathology and Biochemistry, Duke University Medical Center, Durham, North Carolina, U.S.A. S V Pizzo The Departments of Pathology and Biochemistry, Duke University Medical Center, Durham, North Carolina, U.S.A. Recommend Article Abstract PDF Download(opens in new window) Buy Article(opens in new window) Summary Radiolabeled α2-antiplasmin cleared slowly from the circulation of mice. Complex formation with either plasmin or trypsin resulted in a significant increase in the plasma elimination rate of the protease inhibitor. Approximately 20 min and 14 min were required for 50% of the injected α2-antiplasmin-plasmin and α2-antiplasmin-trypsin to clear from the circulation, respectively. Significant competition was observed when radiolabeled α2-antiplasmin-plasmin was cleared in the presence of a large molar excess of unlabeled α2-antiplasmin-plasmin. α1-Antitrypsin-trypsin failed to compete with radiolabeled α2-antiplasmin-plasmin even when present at 2000 fold molar excess. Organ distribution studies localized the major site of α2-antiplasmin-plasmin clearance in the liver. Microscopic autoradiography data suggested that the cell responsible for the clearance pathway was the hepatocyte. Keywords Keywordsα2-antiplasimn - α2-antitrypsin - Protease inhibitor - plasmin(ogen) - Clearance PDF (605 kb) References References 1 Collen D. On the regulation and control of fibrinolysis. Thromb Haemostas 1980; 43: 77-89 2 Aoki N. Natural inhibitors of fibrinolysis. Prog Cardiovasc Dis 1979; 21: 267-286 3 Moroi M, Aoki N. Isolation and characterization of α2-plasmin inhibitor. J Biol Chem 1976; 251: 5956-5965 4 Mullertz S, Clemmensen I. The primary inhibitor of plasmin in human plasma. Biochem J 1976; 159: 543-553 5 Wiman B, Collen D. Purification and characterization of human antiplasmin, the fast acting plasmin inhibitor in plasma. Eur J Biochem 1977; 78: 19-26 6 Aoki N, Moroi M, Matsuda M, Tachiya K. The behavior of α2-plasmin inhibitor in fibrinolytic states. J Clin Invest 1977; 60: 361-369 7 Collen D, Verstraete M. α2-antiplasmin consumption and fibrinogen breakdown during thrombolytic therapy. Thromb Res 1979; 14: 631-639 8 Wiman B, Collen D. On the mechanism of the reaction between human α2-antiplasmin and plasmin. J Biol Chem 1979; 254: 9291-9297 9 Harpel PC. Plasmin inhibitor interactions: the effectiveness of α2-plasmin inhibitor in the presence of α2-macroglobulin. J Exp Med 1977; 146: 1033-1040 10 Collen D, Wiman B. Turnover of antiplasmin, the fast-acting plasmin inhibitor of plasma. Blood 1979; 53: 313-324 11 Gonias SL, Einarsson M, Pizzo SV. Catabolic pathways for streptokinase, plasmin and streptokinase activator complex in mice. J Clin Invest 1982; 70: 412-423 12 Imber MJ, Pizzo SV. Clearance and binding of two electrophoretic forms of human α2-macroglobulin. J Biol Chem 1981; 256: 8134-8139 13 Ohlsson K. Elimination of 125I-trypsin α2-macroglobulin complexes from blood by reticuloendothelial cells in dog. Acta Physiol Scand 1971; 81: 269-272 14 Fuchs HE, Shifman MA, Pizzo SV. In vivo catabolism of α2-proteinase inhibitor-trypsin, antithrombin III-thrombin and α2-macroglobulin-methylamine. Biochim Biophys Acta 1982; 716: 151-157 15 Shifman MA, Pizzo SV. The in vivo metabolism of antithrombin III and antithrombin III complexes. J Biol Chem 1982; 257: 3243-3248 16 Deutsch DG, Mertz ET. Plasminogen: purification from human plasma by affinity chromatography. Science 1970; 170: 1095-1096 17 Brockway WJ, Castellino FJ. Measurement of the binding of antifibrinolytic amino acids to various plasminogens. Arch Biochem Biophys 1972; 151: 194-199 18 Violand BN, Castellino FJ. Mechanism of the urokinase catalyzed activation of human plasminogen. J Biol Chem 1976; 251: 3906-3912 19 Pannell R, Johnson D, Travis J. Isolation and properties of human plasma α-1-protease inhibitor. Biochemistry 1974; 13: 5439-5445 20 Chase T, Shaw E. p-Nitrophenyl-p’-guanidinobenzoate HCl: a new active site titrant for trypsin. Biochem Biophys Res Commun 1967; 29: 508-514 21 Sjoholm I, Wiman B, Wallen P. Studies on the conformational changes of plasminogen induced during activation to plasmin and by 6-Aminohexanoic acid. Eur J Biochem 1973; 39: 471-479 22 David GS, Reisfeld RC. Protein iodination with solid state lactoperoxidase. Biochemistry 1974; 13: 1014-1021 23 Humason GL. In Animal Tissue Techniques. 515-525 W H Freeman Co; San Francisco: 1972 24 Marynen P, VanLeuven F, Cassiman J-J, VanDenBerghe H. A monoclonal antibody to a neo-antigen on α2-macroglobulin complexes inhibits receptor-mediated endocytosis. J Immunol 1981; 127: 1782-1786
