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Mechanisms for the involvement of high molecular weight kininogen in surface-dependent reactions of Hageman factor

Academic Article
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Overview

authors

  • Griffin, John
  • Cochrane, Charles

publication date

  • 1976

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • The mechanisms by which human high molecular weight kininogen (HMKrK) contributes to the surface-dependent activation of the Hageman factor systems have been studied. The ability of various mixtures of purified human Hageman factor (coagulation factor XII), HMrK, prekallikrein, and kaolin to activate coagulation factor XI was determined with factor XIa (activated factor XI) clotting assays. Hageman factor, HMrK and prekallikrein were required for maximal rates of activation of factor XI. A certain optimal mixture of purified Hageman factor, HMrK, prekallikrein, and kaolin gave the same rapid initial rate of activation of purified factor XI as an equivalent aliquot of factor XI-deficient plasma. This suggests that potent, surface-mediated activation of factor XI in plasma is explicable in terms of Hageman factor, HMrK, and prekallikrein. By studying separately some of the surface-dependent reactions involving Hageman factor, it was found that HMrK accelerated by at least an order of magnitude the following reactions: (i) the activation of factor XI by activated Hageman factor; (ii) the activation of prekallikrein by activated Hageman factor; and (iii) the activation of Hageman factor by kallikrein. Stoichiometric rather than catalytic amounts of HMrK gave optimal activation of factor XI. These results are consistent with the hypothesis that HMrK and Hageman factor form a complex on kaolin which renders Hageman factor more susceptible to proteolytic activation by kallikrein and which facilitates the action of activated Hageman factor on its substrate proteins, factor XI and prekallikrein.

subject areas

  • Blood Coagulation
  • Factor XI
  • Factor XII
  • Kallikreins
  • Kaolin
  • Kininogens
  • Models, Biological
  • Molecular Weight
  • Prekallikrein
  • Solubility
  • Trypsin
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Identity

PubMed Central ID

  • PMC430686

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.73.8.2554

PubMed ID

  • 1066663
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Additional Document Info

start page

  • 2554

end page

  • 2558

volume

  • 73

issue

  • 8

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