• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Feb 1980; 65(2): 413–421.
PMCID: PMC371379

Function and Immunochemistry of Prekallikrein-High Molecular Weight Kininogen Complex in Plasma

Abstract

Plasma from individuals with high molecular weight (HMW) kininogen deficiency has been reported to be deficient in prekallikrein as measured by radial immunodiffusion, prekallikrein coagulant activity, and/or kaolin-activated arginine esterase activity. The discovery that prekallikrein and HMW kininogen circulate as a complex in plasma led us to reevaluate the antigenic and functional properties of prekallikrein in HMW kininogen-deficient plasma as well as in normal plasma.

The low prekallikrein antigen level in an individual with HMW kininogen deficiency was corrected to the normal range (80-95%) by the addition of 0.2 U/ml of purified HMW kininogen. A similar increase in apparent prekallikrein antigen was observed when purified prekallikrein and HMW kininogen were combined. The correction of the apparent prekallikrein defect in this HMW kininogen-deficient plasma coincided with the formation of a prekallikrein-HMW kininogen complex as demonstrated by immunoelectrophoresis. Similar findings were demonstrated with purified prekallikrein and HMW kininogen by immunoelectrophoresis as well as crossed immunoelectrophoresis.

The coagulant activity in HMW kininogen-deficient plasma was increased in a dose-dependent manner by the addition of HMW kininogen, reaching 85% of normal level at a concentration of 0.2 U/ml. Kaolin-activated arginine esterase activity (kallikrein) in HMW kininogen-deficient plasma was fully corrected when HMW kininogen was added to the deficient plasma after depletion of kallikrein inhibitors. The functional and antigenic concentration of prekallikrein in plasma from four other HMW kininogen-deficient individuals was similarly corrected to normal after adding HMW kininogen.

Addition of HMW kininogen increased the apparent prekallikrein activity in native normal plasma (as measured by esterase activity) but not in normal plasma in which inhibitors were inactivated. The apparent prekallikrein antigen concentration (as measured by radial immunodiffusion or electroimmunodiffusion) increased upon addition of HMW kininogen. Immunoelectrophoresis as well as gel filtration of normal plasma revealed the presence of free prekallikrein (17-38% of the total) in addition to the HMW kininogen-prekallikrein complex previously reported.

This study emphasizes the influence of HMW kininogen on both functional and immunologic determinations of prekallikrein.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Colman RW, Bagdasarian A, Talamo RC, Scott CF, Seavey M, Guimaraes JA, Pierce JV, Kaplan AP. Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways. J Clin Invest. 1975 Dec;56(6):1650–1662. [PMC free article] [PubMed]
  • Saito H, Ratnoff OD, Waldmann R, Abraham JP. Fitzgerald Trait: Deficiency of a Hitherto Unrecognized Agent, Fitzgerald Factor, Participating in Surface-Mediated Reactions of Clotting, Fibrinolysis, Generation of Kinins, and the Property of Diluted Plasma Enhancing Vascular Permeability (PF/Dil). J Clin Invest. 1975 May;55(5):1082–1089. [PMC free article] [PubMed]
  • Wuepper KD, Miller DR, Lacombe MJ. Flaujeac trait. Deficiency of human plasma kininogen. J Clin Invest. 1975 Dec;56(6):1663–1672. [PMC free article] [PubMed]
  • Donaldson VH, Glueck HI, Miller MA, Movat HZ, Habal F. Kininogen deficiency in Fitzgerald trait: role of high molecular weight kininogen in clotting and fibrinolysis. J Lab Clin Med. 1976 Feb;87(2):327–337. [PubMed]
  • Griffin JH, Cochrane CG. 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. [PMC free article] [PubMed]
  • Meier HL, Pierce JV, Colman RW, Kaplan AP. Activation and function of human Hageman factor. The role of high molecular weight kininogen and prekallikrein. J Clin Invest. 1977 Jul;60(1):18–31. [PMC free article] [PubMed]
  • Liu CY, Scott CF, Bagdasarian A, Pierce JV, Kaplan AP, Colman RW. Potentiation of the function of Hageman factor fragments by high molecular weight kininogen. J Clin Invest. 1977 Jul;60(1):7–17. [PMC free article] [PubMed]
  • Scott CF, Liu CY, Colman RW. Human plasma prekallikrein: a rapid high-yield method for purification. Eur J Biochem. 1979 Oct;100(1):77–83. [PubMed]
  • 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]
  • Habal FM, Movat HZ. Rapid purification of human high molecular weight kininogen. Agents Actions. 1976 Sep;6(5):565–568. [PubMed]
  • Bagdasarian A, Talamo RC, Colman RW. Isolation of high molecular weight activators of human plasma prekallikrein. J Biol Chem. 1973 May 25;248(10):3456–3463. [PubMed]
  • Bagdasarian A, Lahiri B, Talamo RC, Wong P, Colman RW. Immunochemical studies of plasma kallikrein. J Clin Invest. 1974 Dec;54(6):1444–1454. [PMC free article] [PubMed]
  • Laurell CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem. 1966 Apr;15(1):45–52. [PubMed]
  • Colman RW, Edelman R, Scott CF, Gilman RH. Plasma kallikrein activation and inhibition during typhoid fever. J Clin Invest. 1978 Feb;61(2):287–296. [PMC free article] [PubMed]
  • Mancini G, Carbonara AO, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. [PubMed]
  • SIEGELMAN AM, CARLSON AS, ROBERTSON T. Investigation of serum trypsin and related substances. I. The quantitative demonstration of trypsinlike activity in human blood serum by a micromethod. Arch Biochem Biophys. 1962 Apr;97:159–163. [PubMed]
  • Colman RW, Mason JW, Sherry S. The kallikreinogen-kallikrein enzyme system of human plasma. Assay of components and observations in disease states. Ann Intern Med. 1969 Oct;71(4):763–773. [PubMed]
  • Colman RW, 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. [PMC free article] [PubMed]
  • Kluft C. Determination of prekallikrein in human plasma: optimal conditions for activating prekallikrein. J Lab Clin Med. 1978 Jan;91(1):83–95. [PubMed]
  • PROCTOR RR, RAPAPORT SI. The partial thromboplastin time with kaolin. A simple screening test for first stage plasma clotting factor deficiencies. Am J Clin Pathol. 1961 Sep;36:212–219. [PubMed]
  • Mandle RJ, Colman RW, Kaplan AP. Identification of prekallikrein and high-molecular-weight kininogen as a complex in human plasma. Proc Natl Acad Sci U S A. 1976 Nov;73(11):4179–4183. [PMC free article] [PubMed]
  • IVERSEN T, BASTRUP-MADSEN P. Congenital familial deficiency of factor V (parahaemophilia) combined with deficiency of antihaemophilic globulin. Br J Haematol. 1956 Jul;2(3):265–275. [PubMed]
  • Green D, Chediak JR. von Willebrand's disease: current concepts. Am J Med. 1977 Mar;62(3):315–318. [PubMed]
  • Donaldson VH, Kleniewski J, Saito H, Sayed JK. Prekallikrein deficiency in a kindred with kininogen deficiency and Fitzgerald trait clotting defect. Evidence that high molecular weight kininogen and prekallikrein exist as a complex in normal human plasma. J Clin Invest. 1977 Sep;60(3):571–583. [PMC free article] [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...