Original article| Volume 102, ISSUE 4, P487-499, October 1983

The role of prekallikrein and high-molecular-weight kininogen in the contact activation of Hageman factor (factor XII) by sulfatides and other agents

  • Francisco España
    From Ciudad Sanitaria “La Fe,” Centro de Investigation, Unidad de Bioquiraica, Valencia, Spain

    The Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio, USA
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  • Oscar D. Ratnoff
    Reprint requests: Oscar D. Ratnoff, M.D., University Hospitals of Cleveland, Cleveland, Ohio 44106.
    From Ciudad Sanitaria “La Fe,” Centro de Investigation, Unidad de Bioquiraica, Valencia, Spain

    The Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio, USA
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  • Author Footnotes
    1 Dr. Ratnoff is a Career Investigator of the American Heart Association.
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      Hageman factor (HF, factor XII), adsorbed to negatively charged agents, is transformed to an activated state in which it initiates reactions of the intrinsic pathway of thrombin formation by activating plasma thromboplastin antecedent (PTA, factor XI). High-molecular-weight kininogen (HMWK, Fitzgerald factor) and plasma prekallikrein accelerate these early steps in the clotting process. Questions have been raised about the role of HMWK in the activation of Hageman factor by surfaces. In the present studies, we report that the activation of purified human HF by sulfatides, ellagic acid, kaolin, or glass occurred in the absence of HMWK. Indeed, small amounts of HMWK inhibited activation of HF by ellagic acid. Physiological concentration of HMWK had little or no influence on the activation of HF by sulfatides, kaolin, or glass, but higher concentrations (3 to 6 times more) showed the same inhibitory effect as after activation by ellagic acid. This inhibitory property of HMWK may be attributed to competitive binding of HF and HMWK on the surface of the activating agents. In fact, when HF was added to kaolin or glass that had been incubated with HMWK and then washed, the inhibitory effect persisted, indicating HMWK that was bound to the surface blocked activation of HF. Studies with 125I-HF and 125I-HMWK supported this interpretation. Plasma prekallikrein accelerated activation of the amidolytic properties of HF by sulfatides, kaolin, or glass but did not influence activation of HF by ellagic acid. In the presence of plasma kallikrein, HMWK at moderate concentrations slightly accelerated the rate of activation of HF by activating agents other than ellagic acid. Higher concentrations of HMWK counteracted both the accelerating effect of prekallikrein and the inhibitory effect observed when HF was incubated with an excess of kaolin. These experiments, then, support the view that the procoagulant function of HMWK is localized to a point subsequent to the activation of HF.


      Hageman factor or factor XII ((HF)), plasma thromboplastin antecedent or factor XI ((PTA)), high-molecular-weight kininogen or Fitzgerald factor ((HMWK)), soybean trypsin inhibitor ((SBTI)), ovomucoid trypsin inhibitor ((OTI)), di-isopropylfluorophosphate ((DFP)), H-d-prolyl-l-phenylalanyl-l-arginine-p-nitroanilide ((HPPAN S-2302)), sodium dodecylsulfate-polyacrylamide gel electrophoresis ((SDS-PAGE)), barbital-saline buffer ((BS)), tris-(hydroxymethyl)-aminomethane ((Tris)), sodium ethylenediaminetetraacetic acid ((EDTA)), p-nitroaniline ((p-NA)), molecular weight ((MW)), diethylaminoethyl ((DEAE)), carboxymethyl ((CM))
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