title: Polyphosphate as modulator of hemostasis, thrombosis, and inflammation.
abstract: Inorganic polyphosphate (polyP), a linear polymer of phosphates, is present in many infectious microorganisms and is secreted by mast cells and platelets. PolyP has recently been shown to accelerate blood clotting and slow fibrinolysis, in a manner that is highly dependent on polymer length. Very long-chain polyP (of the type present in microorganisms) is an especially potent trigger of the contact pathway, enhances the proinflammatory activity of histones, and may participate in host responses to pathogens. PolyP also inhibits complement, providing another link between polyP and inflammation/innate immunity. Platelet-size polyP (which is considerably shorter) accelerates factor V activation, opposes the anticoagulant action of tissue factor pathway inhibitor, modulates fibrin clot structure, and promotes factor XI activation. PolyP may have utility in treating bleeding. It is also a potential target for the development of antithrombotic drugs with a novel mechanism of action and potentially fewer bleeding side effects compared with conventional anticoagulants.
authors.affiliation: Biochemistry Department, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: J H
authors.identifier: http://orcid.org/0000-0002-1570-1569
authors.initials: JH
authors.lastname: Morrissey
authors.affiliation: Biochemistry Department, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Smith
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D011122:Polyphosphates / Q000097:blood*; D015398:Signal Transduction; D013927:Thrombosis / Q000097:blood* / Q000188:drug therapy / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D018836:Inflammation Mediators; D011122:Polyphosphates
keywords: blood coagulation; coagulation factor XI; inflammation; kallikrein‐kinin system; platelets; polyphosphates