Polyphosphate modulates blood coagulation and fibrinolysis

被引:448
作者
Smith, SA
Mutch, NJ
Baskar, D
Rohloff, P
Docampo, R [1 ]
Morrissey, JH
机构
[1] Univ Illinois, Coll Med, Dept Biochem, Urbana, IL 61801 USA
[2] Univ Illinois, Coll Vet Med, Dept Pathobiol, Urbana, IL 61801 USA
关键词
factor V; platelets; tissue factor pathway inhibitor; acidocalcisomes; dense granules;
D O I
10.1073/pnas.0507195103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Inorganic polyphosphate is an abundant component of acidocalcisomes of bacteria and unicellular eukaryotes. Human platelet dense granules strongly resemble acidocalcisomes, and we recently showed that they contain substantial amounts of polyphosphate, which is secreted upon platelet activation. We now report that polyphosphate is a potent hemostatic regulator, accelerating blood clotting by activating the contact pathway and promoting the activation of factor V, which in turn results in abrogation of the function of the natural anticoagulant protein, tissue factor pathway inhibitor. Polyphosphate was also found to delay clot lysis by enhancing a natural antifibrinolytic agent, thrombin-activatable fibrinolysis inhibitor. Polyphosphate is unstable in blood or plasma, owing to the presence of phosphatases. We propose that polyphosphate released from platelets or microorganisms initially promotes clot formation and stability; subsequent degradation of polyphosphate by blood phosphatases fosters inhibition of clotting and activation of fibrinolysis during wound healing.
引用
收藏
页码:903 / 908
页数:6
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