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 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. › Author Affiliations Recommend Article Abstract PDF Download Buy Article 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
