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. 1974 Nov 30;140(6):1615–1630. doi: 10.1084/jem.140.6.1615

SUBSTRATES OF HAGEMAN FACTOR

I. Isolation and Characterization of Human Factor XI (PTA) and Inhibition of the Activated Enzyme by α1-Antitrypsin

Louis W Heck 1, Allen P Kaplan 1
PMCID: PMC2139762  PMID: 4547783

Abstract

Unactivated partial thromboplastin antecedent (PTA) has been purified by sequential chromatography of plasma on quaternary aminoethyl Sephadex, sulphoprophyl Sephadex, Sephadex G-150, and passage over an anti-IgG immunoadsorbant. The preparation gave a single band after alkaline disc gel electrophoresis, sodium dodecyl sulfate (SDS) gel electrophoresis and isoelectric focusing in acrylamide gels and was found to have a mol wt of 175,000 by gel filtration, 163,000 by SDS gel electrophoresis, and an isoelectric point of 8.8–9.4 (peak 9.0–9.1). Pre-PTA was activated directly by activated Hageman factor or by Hageman factor prealbumin fragments. Its coagulant activity was inhibited by DFP, soybean trypsin inhibitor and trasylol but not by lima bean trypsin inhibitor or ovomucoid trypsin inhibitor indicating that activated PTA possesses the same inhibition profile utilizing these reagents as does plasma kallikrein. A major plasma inhibitor of activated PTA was found to be a 65,000 mol wt α-globulin which was isolated free of α1-chymotrypsin inhibitor, inter α-trypsin inhibitor, α2-macroglobulin, and the other known inhibitors of activated PTA, the activated first component of complement (C1 INH), and antithrombin III. Its physicochemical properties were identical to α1-antitrypsin, and it was absent in α1-antitrypsin-deficient plasma thereby identifying this PTA inhibitor as α1-antitrypsin.

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Selected References

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  1. Amir J., Ratnoff O. D., Pensky J. Partial purification and some properties of a plasma inhibitor of activated plasma thromboplastin antecedent (factor XI). J Lab Clin Med. 1972 Dec;80(6):786–802. [PubMed] [Google Scholar]
  2. Cochrane C. G., Revak S. D., Wuepper K. D. Activation of Hageman factor in solid and fluid phases. A critical role of kallikrein. J Exp Med. 1973 Dec 1;138(6):1564–1583. doi: 10.1084/jem.138.6.1564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Damus P. S., Hicks M., Rosenberg R. D. Anticoagulant action of heparin. Nature. 1973 Dec 7;246(5432):355–357. doi: 10.1038/246355a0. [DOI] [PubMed] [Google Scholar]
  4. Deutsch D. G., Mertz E. T. Plasminogen: purification from human plasma by affinity chromatography. Science. 1970 Dec 4;170(3962):1095–1096. doi: 10.1126/science.170.3962.1095. [DOI] [PubMed] [Google Scholar]
  5. Forbes C. D., Pensky J., Ratnoff O. D. Inhibition of activated Hageman factor and activated plasma thromboplastin antecedent by purified serum C1 inactivator. J Lab Clin Med. 1970 Nov;76(5):809–815. [PubMed] [Google Scholar]
  6. Harpel P. C. Separation of plasma thromboplastin antecedent from kallikrein by the plasma 2 -macroglobulin, kallikrein inhibitor. J Clin Invest. 1971 Oct;50(10):2084–2090. doi: 10.1172/JCI106702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kaplan A. P., Austen K. F. A pre-albumin activator of prekallikrein. J Immunol. 1970 Oct;105(4):802–811. [PubMed] [Google Scholar]
  8. Kaplan A. P., Austen K. F. A prealbumin activator of prekallikrein. II. Derivation of activators of prekallikrein from active Hageman factor by digestion with plasmin. J Exp Med. 1971 Apr 1;133(4):696–712. doi: 10.1084/jem.133.4.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kaplan A. P., Austen K. F. The fibrinolytic pathway of human plasma. Isolation and characterization of the plasminogen proactivator. J Exp Med. 1972 Dec 1;136(6):1378–1393. doi: 10.1084/jem.136.6.1378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kaplan A. P., Kay A. B., Austen K. F. A prealbumin activator of prekallikrein. 3. Appearance of chemotactic activity for human neutrophils by the conversion of human prekallikrein to kallikrein. J Exp Med. 1972 Jan;135(1):81–97. doi: 10.1084/jem.135.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Liener I. E., Garrison O. R., Pravda Z. The purification of human serum 1 -antitrypsin by affinity chromatography on concanavalin A. Biochem Biophys Res Commun. 1973 Mar 17;51(2):436–443. doi: 10.1016/0006-291x(73)91276-x. [DOI] [PubMed] [Google Scholar]
  12. McConnell D. J. Inhibitors of kallikrein in human plasma. J Clin Invest. 1972 Jul;51(7):1611–1623. doi: 10.1172/JCI106962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. NOSSEL H. L., NIEMETZ J. A NORMAL INHIBITOR OF THE BLOOD COAGULATION CONTACT REACTION PRODUCT. Blood. 1965 May;25:712–723. [PubMed] [Google Scholar]
  14. Niemetz J., Nossel H. L. Method of purification and properties of anti-XIa (inhibitor of the contact product). Thromb Diath Haemorrh. 1967 May 31;17(3-4):335–348. [PubMed] [Google Scholar]
  15. RATNOFF O. D., DAVIE E. W., MALLETT D. L. Studies on the action of Hageman factor: evidence that activated Hageman factor in turn activates plasma thromboplastin antecedent. J Clin Invest. 1961 May;40:803–819. doi: 10.1172/JCI104314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ratnoff O. D., Pensky J., Donaldson V. H., Amir J. The inhibitory properties of plasma against activated plasma thromboplastin antecedent (factor XIa) in hereditary angioneurotic edema. J Lab Clin Med. 1972 Dec;80(6):803–809. [PubMed] [Google Scholar]
  17. Ratnoff O. D. Studies on the product of the reaction between activated Hageman factor (factor XII) and plasma thromboplastin antecedent (factor XI). J Lab Clin Med. 1972 Nov;80(5):704–710. [PubMed] [Google Scholar]
  18. Saito H., Ratnoff O. D., Marshall J. S., Pensky J. Partial purification of plasma thromboplastin antecedent (factor XI) and its activation by trypsin. J Clin Invest. 1973 Apr;52(4):850–861. doi: 10.1172/JCI107249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schiffman S., Lee P. Preparation, characterization, and activation of a highly purified factor XI: evidence that a hitherto unrecognized plasma activity participates in the interaction of factors XI and XII. Br J Haematol. 1974 May;27(1):101–114. doi: 10.1111/j.1365-2141.1974.tb06778.x. [DOI] [PubMed] [Google Scholar]
  20. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
  21. Weiss A. S., Gallin J. I., Kaplan A. P. Fletcher factor deficiency. A diminished rate of Hageman factor activation caused by absence of prekallikrein with abnormalities of coagulation, fibrinolysis, chemotactic activity, and kinin generation. J Clin Invest. 1974 Feb;53(2):622–633. doi: 10.1172/JCI107597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wuepper K. D. Prekallikrein deficiency in man. J Exp Med. 1973 Dec 1;138(6):1345–1355. doi: 10.1084/jem.138.6.1345. [DOI] [PMC free article] [PubMed] [Google Scholar]

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