Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Aug;80(2):582–585. doi: 10.1172/JCI113108

Protection by recombinant alpha 1-antitrypsin Ala357 Arg358 against arterial hypotension induced by factor XII fragment.

M Schapira, M A Ramus, B Waeber, H R Brunner, S Jallat, D Carvallo, C Roitsch, M Courtney
PMCID: PMC442273  PMID: 3497179

Abstract

The specificity of serpin superfamily protease inhibitors such as alpha 1-antitrypsin or C1 inhibitor is determined by the amino acid residues of the inhibitor reactive center. To obtain an inhibitor that would be specific for the plasma kallikrein-kinin system enzymes, we have constructed an antitrypsin mutant having Arg at the reactive center P1 residue (position 358) and Ala at residue P2 (position 357). These modifications were made because C1 inhibitor, the major natural inhibitor of kallikrein and Factor XIIa, contains Arg at P1 and Ala at P2. In vitro, the novel inhibitor, alpha 1-antitrypsin Ala357 Arg358, was more efficient than C1 inhibitor for inhibiting kallikrein. Furthermore, Wistar rats pretreated with alpha 1-antitrypsin Ala357 Arg358 were partially protected from the circulatory collapse caused by the administration of beta-Factor XIIa.

Full text

PDF
585

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alving B. M., Hojima Y., Pisano J. J., Mason B. L., Buckingham R. E., Jr, Mozen M. M., Finlayson J. S. Hypotension associated with prekallikrein activator (Hageman-factor fragments) in plasma protein fraction. N Engl J Med. 1978 Jul 13;299(2):66–70. doi: 10.1056/NEJM197807132990203. [DOI] [PubMed] [Google Scholar]
  2. Bock S. C., Skriver K., Nielsen E., Thøgersen H. C., Wiman B., Donaldson V. H., Eddy R. L., Marrinan J., Radziejewska E., Huber R. Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization. Biochemistry. 1986 Jul 29;25(15):4292–4301. doi: 10.1021/bi00363a018. [DOI] [PubMed] [Google Scholar]
  3. Burger D., Schleuning W. D., Schapira M. Human plasma prekallikrein. Immunoaffinity purification and activation to alpha- and beta-kallikrein. J Biol Chem. 1986 Jan 5;261(1):324–327. [PubMed] [Google Scholar]
  4. Colman R. W. Surface-mediated defense reactions. The plasma contact activation system. J Clin Invest. 1984 May;73(5):1249–1253. doi: 10.1172/JCI111326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Colman R. W., Wachtfogel Y. T., Kucich U., Weinbaum G., Hahn S., Pixley R. A., Scott C. F., de Agostini A., Burger D., Schapira M. Effect of cleavage of the heavy chain of human plasma kallikrein on its functional properties. Blood. 1985 Feb;65(2):311–318. [PubMed] [Google Scholar]
  6. Courtney M., Jallat S., Tessier L. H., Benavente A., Crystal R. G., Lecocq J. P. Synthesis in E. coli of alpha 1-antitrypsin variants of therapeutic potential for emphysema and thrombosis. Nature. 1985 Jan 10;313(5998):149–151. doi: 10.1038/313149a0. [DOI] [PubMed] [Google Scholar]
  7. Davis A. E., 3rd, Whitehead A. S., Harrison R. A., Dauphinais A., Bruns G. A., Cicardi M., Rosen F. S. Human inhibitor of the first component of complement, C1: characterization of cDNA clones and localization of the gene to chromosome 11. Proc Natl Acad Sci U S A. 1986 May;83(10):3161–3165. doi: 10.1073/pnas.83.10.3161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Griffin J. H., Cochrane C. G. Mechanisms for the involvement of high molecular weight kininogen in surface-dependent reactions of Hageman factor. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2554–2558. doi: 10.1073/pnas.73.8.2554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jallat S., Carvallo D., Tessier L. H., Roecklin D., Roitsch C., Ogushi F., Crystal R. G., Courtney M. Altered specificities of genetically engineered alpha 1 antitrypsin variants. Protein Eng. 1986 Oct-Nov;1(1):29–35. doi: 10.1093/protein/1.1.29. [DOI] [PubMed] [Google Scholar]
  10. KITZ R., WILSON I. B. Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J Biol Chem. 1962 Oct;237:3245–3249. [PubMed] [Google Scholar]
  11. Marks E., Hojima Y., Frech M. E., Keiser H., Pisano J. J. An inhibitor from corn blocks the hypotensive action of plasma protein fraction and active Hageman factor. Thromb Res. 1981 Jul 1;23(1-2):97–102. doi: 10.1016/0049-3848(81)90242-5. [DOI] [PubMed] [Google Scholar]
  12. Nagase H., Barrett A. J. Human plasma kallikrein. A rapid purification method with high yield. Biochem J. 1981 Jan 1;193(1):187–192. doi: 10.1042/bj1930187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Owen M. C., Brennan S. O., Lewis J. H., Carrell R. W. Mutation of antitrypsin to antithrombin. alpha 1-antitrypsin Pittsburgh (358 Met leads to Arg), a fatal bleeding disorder. N Engl J Med. 1983 Sep 22;309(12):694–698. doi: 10.1056/NEJM198309223091203. [DOI] [PubMed] [Google Scholar]
  14. RATNOFF O. D., LEPOW I. H. Some properties of an esterase derived from preparations of the first component of complement. J Exp Med. 1957 Aug 1;106(2):327–343. doi: 10.1084/jem.106.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Regoli D., Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980 Mar;32(1):1–46. [PubMed] [Google Scholar]
  16. Revak S. D., Cochrane C. G., Johnston A. R., Hugli T. E. Structural changes accompanying enzymatic activation of human Hageman factor. J Clin Invest. 1974 Sep;54(3):619–627. doi: 10.1172/JCI107799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schapira M. Major inhibitors of the contact phase coagulation factors. Semin Thromb Hemost. 1987 Jan;13(1):69–78. doi: 10.1055/s-2007-1003476. [DOI] [PubMed] [Google Scholar]
  18. Schapira M., Ramus M. A., Jallat S., Carvallo D., Courtney M. Recombinant alpha 1-antitrypsin Pittsburgh (Met 358----Arg) is a potent inhibitor of plasma kallikrein and activated factor XII fragment. J Clin Invest. 1986 Feb;77(2):635–637. doi: 10.1172/JCI112347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schapira M., Scott C. F., Colman R. W. Protection of human plasma kallikrein from inactivation by C1 inhibitor and other protease inhibitors. The role of high molecular weight kininogen. Biochemistry. 1981 May 12;20(10):2738–2743. doi: 10.1021/bi00513a006. [DOI] [PubMed] [Google Scholar]
  20. Scott C. F., Carrell R. W., Glaser C. B., Kueppers F., Lewis J. H., Colman R. W. Alpha-1-antitrypsin-Pittsburgh. A potent inhibitor of human plasma factor XIa, kallikrein, and factor XIIf. J Clin Invest. 1986 Feb;77(2):631–634. doi: 10.1172/JCI112346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Thompson R. E., Mandle R., Jr, Kaplan A. P. Characterization of human high molecular weight kininogen. Procoagulant activity associated with the light chain of kinin-free high molecular weight kininogen. J Exp Med. 1978 Feb 1;147(2):488–499. doi: 10.1084/jem.147.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Travis J., Matheson N. R., George P. M., Carrell R. W. Kinetic studies on the interaction of alpha 1-proteinase inhibitor (Pittsburgh) with trypsin-like serine proteinases. Biol Chem Hoppe Seyler. 1986 Sep;367(9):853–859. doi: 10.1515/bchm3.1986.367.2.853. [DOI] [PubMed] [Google Scholar]
  23. Wiggins R. C. Kinin release from high molecular weight kininogen by the action of Hageman factor in the absence of kallikrein. J Biol Chem. 1983 Jul 25;258(14):8963–8970. [PubMed] [Google Scholar]
  24. Wiman B., Collen D. On the kinetics of the reaction between human antiplasmin and plasmin. Eur J Biochem. 1978 Mar 15;84(2):573–578. doi: 10.1111/j.1432-1033.1978.tb12200.x. [DOI] [PubMed] [Google Scholar]
  25. de Agostini A., Lijnen H. R., Pixley R. A., Colman R. W., Schapira M. Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor. J Clin Invest. 1984 Jun;73(6):1542–1549. doi: 10.1172/JCI111360. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES