The autoactivation of Factor XII ( Hageman factor ) induced by low - iMr heparin and dextran sulphate
نویسنده
چکیده
Human Factor XII is known to undergo autoactivation in the presence of dextran sulphate of Mr 500000. We have now studied the dependence of this reaction on the Mr of the dextran sulphate by using fractions resolved by gel filtration. We have found that autoactivation can be induced by dextran sulphate fractions with Mr as-low as 3000, and there is a marked dependence of the rate constant of autoactivation on the Mr value. Fractions with Mr below 8000 gave very low rates of autoactivation; there was a sharp increase in the rate obtained when the Mr of the dextran sulphate was greater than 10000. Various preparations of heparin were also able to support the autoactivation of Factor XII and gave a very similar relationship between molecular size and reaction rate. The data provide support for the hypothesis that the mechanism by which the 'surface' acts in contact activation involves the presence, on the same particle, of multiple binding sites for the proteins.
منابع مشابه
Initiation of contact system activation in plasma is dependent on factor XII autoactivation and not on enhanced susceptibility of factor XII for kallikrein cleavage.
Various mechanisms have been hypothesized to explain the initiation of contact system activation in plasma. We investigated the capability of dextran sulphate (DS) of different molecular weights to initiate contact system activation in normal human plasma, and compared this with their capability to support factor XII autoactivation and to enhance factor XII susceptibility for cleavage by kallik...
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Pro-Phe-Arg chloromethylketone (PPACMK) at 5.26 microM inactivated the amidolytic activity of native human Hageman factor with an apparent first-order rate constant of 0.75 min-1. The activated forms of Hageman factor, Hfa and HFf, were also inactivated by PPACMK with rate constants 0.82 and 0.72 min-1. These numbers indicate that the activity detectable in native Hageman factor is due to conta...
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When purified human blood coagulation Factor XII (Hageman factor) is incubated with sulfatides at 37 degrees C, activation of Factor XII occurs as judged by the appearance of amidolytic activity towards the chromogenic substrate H-D-Pro-Phe-Arg-p-nitroanilide. Polyacrylamide gel electrophoresis studies using 125I-Factor XII as a marker show that the appearance of amidolytic activity correlates ...
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Using components purified from human plasma. we have examined the effects of Cl Inhibitor (CI INH). the primary inhibitor of activated Hageman Factor (HFa) and Hageman factor fragment (HFf). on Hageman Factor (HF) autoactivation. When Hageman factor was exposed to a negatively charged surface. provided by either a glass cuvette or dextran sulfate, the addition of CI INH gave a dosedependent inh...
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