Abstract
The isolation and characterization of the first component of the kinin-forming system in human and rabbit plasma are presented. Functionally, the molecule is the precursor of the activator of prekallikrein (Pre-PKA) and evidence is presented that it is identical with Hageman factor (clotting factor XII). The component from each plasma possessed similar characteristics. This molecule was found to have a mol wt of 110,000 and sedimentation rate of 4.6S. It migrated in electrophoresis as a β-globulin, having an isoelectric point of 6.1. Upon activation with glass, kaolin, diatomaceous earth, ellagic acid, or trypsin, the activated molecule converted purified prekallikrein (prokininogenase) to the active enzyme. Clot-promoting activity was associated with the capacity to activate prekallikrein through each procedure of isolation. The clot-promoting factor was in precursor form, requiring treatment with kaolin or trypsin to gain activity. Evidence indicated that the protein was Hageman factor (factor XII): it promoted clotting of factor XII-deficient, but not Factor XI- or IX-deficient plasma, and did not convert fibrinogen to fibrin it bound to and was activated by kaolin or other negatively charged particles in the presence of chelating agents; the activation by kaolin could be prevented by pretreating the kaolin with hexadimethrine bromide (H Br); prekallikrein-activating and clot-promoting activities were identical in their physical properties; and the prekallikrein activator could not be detected in Hageman factor-deficient plasma. Activation of Hageman factor was accompanied by cleavage of the molecule into several fragments, one of which possessed prekallikrein-activating (PKA) and clot-promoting properties. The PKA fragment sedimented at 2.6S and by gel filtration was found to have a molecular weight of 32,000. The PKA possessed only 1/50 the clot-promoting capacity of the freshly activated native molecule.
Full Text
The Full Text of this article is available as a PDF (1,020.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Colman R. W., Mattler L., Sherry S. Studies on the prekallikrein (kallikreinogen)--kallikrein enzyme system of human plasma. II. Evidence relating the kaolin-activated arginine esterase to plasma kallikrein. J Clin Invest. 1969 Jan;48(1):23–32. doi: 10.1172/JCI105971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- DINIZ C. R., CARVALHO I. F. A micromethod for determination of bradykininogen under several conditions. Ann N Y Acad Sci. 1963 Feb 4;104:77–89. doi: 10.1111/j.1749-6632.1963.tb17654.x. [DOI] [PubMed] [Google Scholar]
- Donaldson V. H., Ratnoff O. D. Hageman factor: alterations in physical properties during activation. Science. 1965 Nov 5;150(3697):754–756. doi: 10.1126/science.150.3697.754. [DOI] [PubMed] [Google Scholar]
- Haanen C., Morselt G., Schoenmakers J. Contact activation of Hageman factor and the interaction of Hageman factor and plasma thromboplastin antecedent. Thromb Diath Haemorrh. 1967 May 31;17(3-4):307–320. [PubMed] [Google Scholar]
- Kaplan A. P., Austen K. F. A pre-albumin activator of prekallikrein. J Immunol. 1970 Oct;105(4):802–811. [PubMed] [Google Scholar]
- 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]
- MARGOLIS J. Activation of plasma by contact with glass: evidence for a common reaction which releases plasma kinin and initiates coagulation. J Physiol. 1958 Nov 10;144(1):1–22. doi: 10.1113/jphysiol.1958.sp006082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MARGOLIS J., BISHOP E. A. Interrelations between different mechanisms of release of biologically active peptides from blood plasma. Nature. 1962 May 26;194:749–751. doi: 10.1038/194749a0. [DOI] [PubMed] [Google Scholar]
- MARGOLIS J., BISHOP E. A. STUDIES ON PLASMA KININS. I. THE COMPOSITION OF KININOGEN COMPLEX. Aust J Exp Biol Med Sci. 1963 Aug;41:293–306. doi: 10.1038/icb.1963.29. [DOI] [PubMed] [Google Scholar]
- MARGOLIS J. Plasma pain-producing substance and blood clotting. Nature. 1957 Dec 28;180(4600):1464–1465. doi: 10.1038/1801464a0. [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]
- Nagasawa S., Takahashi H., Koida M., Suzuki T., Schoenmakers J. G. Partial purification of bovine plasma kallikreinogen, its activation by the Hageman factor. Biochem Biophys Res Commun. 1968 Aug 21;32(4):644–649. doi: 10.1016/0006-291x(68)90287-8. [DOI] [PubMed] [Google Scholar]
- SCHOEMAKERS J., MATZE R., HAANEN C., ZILLIKEN F. PROTEOLYTIC ACTIVITY OF PURIFIED BOVINE HAGEMAN FACTOR. Biochim Biophys Acta. 1964 Nov 8;93:433–436. doi: 10.1016/0304-4165(64)90401-5. [DOI] [PubMed] [Google Scholar]
- WEBSTER M. E., ATNOFF O. D. Role of Hageman factor in the activation of vasodilator activity in human plasma. Nature. 1961 Oct 14;192:180–181. doi: 10.1038/192180a0. [DOI] [PubMed] [Google Scholar]