Abstract
The ability of the two forms of activated Hageman factor (HFa) produced during contact activation of plasma to activate prekallikrein and factor XI was studied. alpha-HFa, defined as an 80,000 mol wt two-chain enzyme which remains bound to the surface was capable of cleaving surface-bound prekallikrein and factor XI. beta-HFa, a 28,000 mol wt single chain molecule, released from the surface during contact activation was able to cleave prekallikrein but showed no activity on factor XI. Cleavage of prekallikrein by beta-HFa occurred irrespective of whether the substrate was surface-bound or in solution. Cleavage of factor XI occurred only when it was surface bound and only the alpha- form of HFa was capable of this proteolytic action. Factor XI was found to remain bound to the surface while prekallikrein and kallikrein rapidly dissociated from the surface into the supernate. These findings suggest that the initiation of intrinsic coagulation through the activation factor XI is a localized event occurring at the site of contact activation and is the result of the action of alpha-HFa. By contrast, kinin generation and fibrinolysis resulting from the formation of kallikrein can be initiated either at the site of contact activation, by alpha-HFa action, or throughout the plasma, by beta-HFa; further dissemination of these activities is assured by the rapid dissociation of kallikrein itself from the surface.
Full Text
The Full Text of this article is available as a PDF (743.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bouma B. N., Griffin J. H. Human blood coagulation factor XI. Purification, properties, and mechanism of activation by activated factor XII. J Biol Chem. 1977 Sep 25;252(18):6432–6437. [PubMed] [Google Scholar]
- David G. S., Reisfeld R. A. Protein iodination with solid state lactoperoxidase. Biochemistry. 1974 Feb 26;13(5):1014–1021. doi: 10.1021/bi00702a028. [DOI] [PubMed] [Google Scholar]
- Griffin J. H., Cochrane C. G. Human factor XII (Hageman factor). Methods Enzymol. 1976;45:56–65. doi: 10.1016/s0076-6879(76)45009-7. [DOI] [PubMed] [Google Scholar]
- Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
- McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
- Revak S. D., Cochrane C. G., Griffin J. H. The binding and cleavage characteristics of human Hageman factor during contact activation. A comparison of normal plasma with plasmas deficient in factor XI, prekallikrein, or high molecular weight kininogen. J Clin Invest. 1977 Jun;59(6):1167–1175. doi: 10.1172/JCI108741. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Wiggins R. C., Bouma B. N., Cochrane C. G., Griffin J. H. Role of high-molecular-weight kininogen in surface-binding and activation of coagulation Factor XI and prekallikrein. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4636–4640. doi: 10.1073/pnas.74.10.4636. [DOI] [PMC free article] [PubMed] [Google Scholar]