Dextran sulphate inhibits phospholipid and sulphatide mediated autoactivation of factor XII.
In normal plasma, high molecular mass dextran sulphate (DS500) induces formation of amidolytic activity towards the chromogenic substrate H-D-Pro-Phe-Arg-p-nitroanilide (S-2302) specific to factor XII and kallikrein. No amidolytic activity was formed when plasma deficient in prekallikrein was exposed to DS500. In contrast, factor XII amidolytic activity was formed upon exposure to sulphatide or acidic phospholipids. To assess whether DS500 interferes with the sulphatide and the acidic phospholipid in activating factor XII, plasma deficient in prekallikrein was incubated with phosphatidylinositol phosphate (PtdInsP) and sulphatide at the conditions necessary for activation with these surfaces and various concentrations of DS500. DS500 inhibited both the PtdInsP and the sulphatide-mediated autoactivation in an antithrombin III independent manner. Heparin also inhibited the PtdInsP mediated autoactivation but not that mediated by sulphatide. The heparin inhibition was due to enhancement of the antithrombin III activity, which could be partly blocked by preincubation of plasma with rabbit anti-human antithrombin III IgG.
Department of Medical Biochemistry, Panum Institute, University of Copenhagen, Denmark.
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I
Schousboe
M S
MS
Rasmussen
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Lintner
D000595:Amino Acid Sequence; D002863:Chromogenic Compounds; D016264:Dextran Sulfate / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005174:Factor XII / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018129:Phosphatidylinositol Phosphates / Q000494:pharmacology*; D011288:Prekallikrein / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000037:antagonists & inhibitors*
D002863:Chromogenic Compounds; D018129:Phosphatidylinositol Phosphates; D013433:Sulfoglycosphingolipids; D005174:Factor XII; D006493:Heparin; D016264:Dextran Sulfate; D011288:Prekallikrein