期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 4, 页码 903-908出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0507195103
关键词
factor V; platelets; tissue factor pathway inhibitor; acidocalcisomes; dense granules
资金
- NHLBI NIH HHS [P50 HL054502, R01 HL047014, R01 HL047014-14A1, HL54502, HL47014] Funding Source: Medline
- NIAID NIH HHS [R01 AI023259, AI23259, R21 AI023259] Funding Source: Medline
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.
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