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. 1970 Mar;49(3):568–575. doi: 10.1172/JCI106267

C[unk] inactivator inhibition by plasmin

Peter C Harpel 1
PMCID: PMC322505  PMID: 4244455

Abstract

Plasmin incubated with partially purified C[unk] inactivator produced a decrease in inhibitory activity which was related to the time of incubation and to the concentration of plasmin. This effect of plasmin was not influenced by the purity of the inhibitor preparations. Soybean trypsin inhibitor and tosyl arginine methyl ester (TAMe), substances which block the active enzymic center of plasmin, prevented the plasmin-induced inactivation. Double diffusion analysis of the functionally deficient, plasmin-treated C[unk] inactivator using a specific antibody, showed a reaction of identity with the untreated inhibitor. Agarose and acrylamide gel immunoelectrophoresis of a plasmin, inhibitor mixture showed the appearance of an additional precipitin band with immunologic reactivity similar to that of the untreated inhibitor. These results demonstrate that plasmin alters both the functional and immunoelectrophoretic properties of C[unk] inactivator, and that the active proteolytic site of plasmin is necessary for this interaction. Since C[unk] inactivator has been shown to inhibit several different proteolytic enzymes including C[unk], kallikrein, PF/Dil, and plasmin, this investigation provides a theoretical relationship between the fibrinolytic, kallikrein, and complement systems which may have pathophysiologic relevance to various human disease states.

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Selected References

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

  1. ALKJAERSIG N., FLETCHER A. P., SHERRY S. xi-Aminocaproic acid: an inhibitor of plasminogen activation. J Biol Chem. 1959 Apr;234(4):832–837. [PubMed] [Google Scholar]
  2. Andrews P. The gel-filtration behaviour of proteins related to their molecular weights over a wide range. Biochem J. 1965 Sep;96(3):595–606. doi: 10.1042/bj0960595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Back N. Fibrinolysin system and vasoactive kinins. Fed Proc. 1966 Jan-Feb;25(1):77–83. [PubMed] [Google Scholar]
  4. Burdon K. L., Queng J. T., Thomas O. C., McGovern J. P. Observations on biochemical abnormalities in hereditary angioneurotic edema. J Allergy. 1965 Nov-Dec;36(6):546–557. doi: 10.1016/0021-8707(65)90192-9. [DOI] [PubMed] [Google Scholar]
  5. DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
  6. DONALDSON V. H., EVANS R. R. A BIOCHEMICAL ABNORMALITY IN HEREDIATRY ANGIONEUROTIC EDEMA: ABSENCE OF SERUM INHIBITOR OF C' 1-ESTERASE. Am J Med. 1963 Jul;35:37–44. doi: 10.1016/0002-9343(63)90162-1. [DOI] [PubMed] [Google Scholar]
  7. DONALDSON V. H., ROSEN F. S. ACTION OF COMPLEMENT IN HEREDITARY ANGIONEUROTIC EDEMA: THE ROLE OF C'1-ESTERASE. J Clin Invest. 1964 Nov;43:2204–2213. doi: 10.1172/JCI105094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Donaldson V. H. Mechanisms of activation of C'1 esterase in hereditary angioneurotic edema plasma in vitro. J Exp Med. 1968 Mar 1;127(3):411–429. doi: 10.1084/jem.127.3.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. EISEN V. FIBRINOLYSIS AND FORMATION OF BIOLOGICALLY ACTIVE POLYPEPTIDES. Br Med Bull. 1964 Sep;20:205–209. doi: 10.1093/oxfordjournals.bmb.a070332. [DOI] [PubMed] [Google Scholar]
  10. Gigli I., Ruddy S., Austen K. F. The stoichiometric measurement of the serum inhibition of the first component of complement by the inhibition of immune hemolysis. J Immunol. 1968 Jun;100(6):1154–1164. [PubMed] [Google Scholar]
  11. HAINES A. L., LEPOW I. H. STUDIES ON HUMAN C'1-ESTERASE. I. PURIFICATION AND ENZYMATIC PROPERTIES. J Immunol. 1964 Mar;92:456–467. [PubMed] [Google Scholar]
  12. Harpel P. The differentiation of esterase and fibrinolytic activity in human plasma euglobulin preparations. Thromb Diath Haemorrh. 1968 Jul 31;19(3):596–598. [PubMed] [Google Scholar]
  13. KAGEN L. J. SOME BIOCHEMICAL AND PHYSICAL PROPERTIES OF THE HUMAN PERMEABILITY GLOBULINS. Br J Exp Pathol. 1964 Dec;45:604–611. [PMC free article] [PubMed] [Google Scholar]
  14. KLINE D. L., FISHMAN J. B. Proactivator function of human plasmin as shown by lysine esterase assay. J Biol Chem. 1961 Oct;236:2807–2812. [PubMed] [Google Scholar]
  15. Klemperer M. R., Donaldson V. H., Rosen F. S. Effect of C'1 esterase on vascular permeability in man: studies in normal and complement-deficient individuals and in patients with hereditary angioneurotic edema. J Clin Invest. 1968 Mar;47(3):604–611. doi: 10.1172/JCI105756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. LANDERMAN N. S., WEBSTER M. E., BECKER E. L., RATCLIFFE H. E. Hereditary angioneurotic edema. II. Deficiency of inhibitor for serum globulin permeability factor and/or plasma kallikrein. J Allergy. 1962 Jul-Aug;33:330–341. doi: 10.1016/0021-8707(62)90032-1. [DOI] [PubMed] [Google Scholar]
  17. LEPOW I. H., PILLEMER L., RATNOFF O. D. The influence of calcium ions on the inactivation of human complement and its components by plasmin. J Exp Med. 1953 Sep;98(3):277–289. doi: 10.1084/jem.98.3.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. LEPOW I. H., RATNOFF O. D., LEVY L. R. Studies on the activation of a proesterase associated with partially purified first component of human complement. J Exp Med. 1958 Mar 1;107(3):451–474. doi: 10.1084/jem.107.3.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. LEPOW I. H., RATNOFF O. D., PILLEMER L. Elution of an esterase from antigen-antibody aggregates treated with human complement. Proc Soc Exp Biol Med. 1956 May;92(1):111–114. doi: 10.3181/00379727-92-22401. [DOI] [PubMed] [Google Scholar]
  20. LEPOW I. H., RATNOFF O. D., ROSEN F. S., PILLEMER L. Observations on a pro-esterase associated with partially purified first component of human complement (C'1). Proc Soc Exp Biol Med. 1956 May;92(1):32–37. doi: 10.3181/00379727-92-22376. [DOI] [PubMed] [Google Scholar]
  21. LEPOW I. H., WURZ L., RATNOFF O. D., PILLEMER L. Studies on the mechanism of inactivation of human complement by plasmin and by antigen-antibody aggregates. I. The requirement for a factor resembling C'1 and the role of Ca++. J Immunol. 1954 Sep;73(3):146–158. [PubMed] [Google Scholar]
  22. LEVY L. R., LEPOW I. H. Assay and properties of serum inhibitor of C'l-esterase. Proc Soc Exp Biol Med. 1959 Aug-Sep;101:608–611. doi: 10.3181/00379727-101-25034. [DOI] [PubMed] [Google Scholar]
  23. Laurell A. B., Lundh B., Malmquist J. Inability of a highly purified streptokinase preparation to inactivate complement in serum. Acta Pathol Microbiol Scand. 1965;64(3):318–328. doi: 10.1111/apm.1965.64.3.318. [DOI] [PubMed] [Google Scholar]
  24. Lundh B., Laurell A. B., Wetterqvist H., White T., Granerus G. A case of hereditary angioneurotic oedema, successfully treated with epsilon-aminocaproic acid. Studies on C'1 esterase inhibitor, C'1 activation, plasminogen level and histamine metabolism. Clin Exp Immunol. 1968 Sep;3(7):733–745. [PMC free article] [PubMed] [Google Scholar]
  25. Mirsky I. A. INHIBITION OF beta HEMOLYTIC STREPTOCOCCI FIBRINOLYSIN BY TRYPSIN INHIBITOR (ANTIPROTEASE). Science. 1944 Sep 1;100(2592):198–200. doi: 10.1126/science.100.2592.198. [DOI] [PubMed] [Google Scholar]
  26. Naff G. B., Ratnoff O. S. The enzymatic nature of C'1r. Conversion of C'1s to C'1 esterase and digestion of amino acid esters by C'1r. J Exp Med. 1968 Oct 1;128(4):571–593. doi: 10.1084/jem.128.4.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. PENSKY J., LEVY L. R., LEPOW I. H. Partial purification of a serum inhibitor of C'1-esterase. J Biol Chem. 1961 Jun;236:1674–1679. [PubMed] [Google Scholar]
  28. PILLEMER L., RATNOFF O. D., BLUM L., LEPOW I. H. The inactivation of complement and its components by plasmin. J Exp Med. 1953 Apr;97(4):573–589. doi: 10.1084/jem.97.4.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pensky J., Schwick H. G. Human serum inhibitor of C'1 esterase: identity with alpha-2-neuraminoglycoprotein. Science. 1969 Feb 14;163(3868):698–699. doi: 10.1126/science.163.3868.698. [DOI] [PubMed] [Google Scholar]
  30. Pickering R. J., Good R. A., Kelly J. R., Gewurz H. Replacement therapy in hereditary angioedema. Successful treatment of two patients with fresh frozen plasma. Lancet. 1969 Feb 15;1(7590):326–330. doi: 10.1016/s0140-6736(69)91295-1. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. ROSEN F. S., PENSKY J., DONALDSON V., CHARACHE P. HEREDITARY ANGIONEUROTIC EDEMA: TWO GENETIC VARIANTS. Science. 1965 May 14;148(3672):957–958. doi: 10.1126/science.148.3672.957. [DOI] [PubMed] [Google Scholar]
  33. Ratnoff O. D., Naff G. B. The conversion of C'IS to C'1 esterase by plasmin and trypsin. J Exp Med. 1967 Feb 1;125(2):337–358. doi: 10.1084/jem.125.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ratnoff O. D., Pensky J., Ogston D., Naff G. B. The inhibition of plasmin, plasma kallikrein, plasma permeability factor, and the C'1r subcomponent of the first component of complement by serum C'1 esterase inhibitor. J Exp Med. 1969 Feb 1;129(2):315–331. doi: 10.1084/jem.129.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  36. SHERRY S., FLETCHER A. P., ALKJAERSIG N. Fibrinolysis and fibrinolytic activity in man. Physiol Rev. 1959 Apr;39(2):343–382. doi: 10.1152/physrev.1959.39.2.343. [DOI] [PubMed] [Google Scholar]
  37. TODD A. S. LOCALIZATION OF FIBRINOLYTIC ACTIVITY IN TISSUES. Br Med Bull. 1964 Sep;20:210–212. doi: 10.1093/oxfordjournals.bmb.a070333. [DOI] [PubMed] [Google Scholar]
  38. TROLL W., SHERRY S., WACHMAN J. The action of plasmin on synthetic substrates. J Biol Chem. 1954 May;208(1):85–93. [PubMed] [Google Scholar]
  39. VONKAULLA K. N. INACTIVATION OF ANTIPLASMIN AND COMPLEMENT C1 IN HUMAN PLASMA RENDERED FIBRINOLYTIC BY SYNTHETIC ORGANIC COMPOUNDS. Thromb Diath Haemorrh. 1963 Nov 1;10:151–163. [PubMed] [Google Scholar]
  40. WARD D. N., ARNOTT M. S. GEL FILTRATION OF PROTEINS, WITH PARTICULAR REFERENCE TO THE GLYCOPROTEIN, LUTEINIZING HORMONE. Anal Biochem. 1965 Aug;12:296–302. doi: 10.1016/0003-2697(65)90094-1. [DOI] [PubMed] [Google Scholar]
  41. Ward P. A. A plasmin-split fragment of C'3 as a new chemotactic factor. J Exp Med. 1967 Aug 1;126(2):189–206. doi: 10.1084/jem.126.2.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Williamson J., Allison A. C. Thin-layer Sephadex chromatography and immunodiffusion. Lancet. 1967 Jul 15;2(7507):123–126. doi: 10.1016/s0140-6736(67)92963-7. [DOI] [PubMed] [Google Scholar]

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