title: Polyphosphate modulates blood coagulation and fibrinolysis.
abstract: 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.
authors.affiliation: Department of Biochemistry, College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Smith
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Mutch
authors.forename: Deepak
authors.initials: D
authors.lastname: Baskar
authors.forename: Peter
authors.initials: P
authors.lastname: Rohloff
authors.forename: Roberto
authors.initials: R
authors.lastname: Docampo
authors.forename: James H
authors.initials: JH
authors.lastname: Morrissey
mesh_terms: D000925:Anticoagulants / Q000737:chemistry; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D025901:Carboxypeptidase B2 / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D005165:Factor V / Q000737:chemistry / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D011122:Polyphosphates / Q000737:chemistry*; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014945:Wound Healing
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D008074:Lipoproteins; D011122:Polyphosphates; C051928:lipoprotein-associated coagulation inhibitor; D005165:Factor V; D025901:Carboxypeptidase B2; D013917:Thrombin