| First Author | Müller F | Year | 2009 |
| Journal | Cell | Volume | 139 |
| Issue | 6 | Pages | 1143-56 |
| PubMed ID | 20005807 | Mgi Jnum | J:157469 |
| Mgi Id | MGI:4430947 | Doi | 10.1016/j.cell.2009.11.001 |
| Citation | Muller F, et al. (2009) Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 139(6):1143-56 |
| abstractText | Platelets play a central role in thrombosis, hemostasis, and inflammation. We show that activated platelets release inorganic polyphosphate (polyP), a polymer of 60-100 phosphate residues that directly bound to and activated the plasma protease factor XII. PolyP-driven factor XII activation triggered release of the inflammatory mediator bradykinin by plasma kallikrein-mediated kininogen processing. PolyP increased vascular permeability and induced fluid extravasation in skin microvessels of mice. Mice deficient in factor XII or bradykinin receptors were resistant to polyP-induced leakage. PolyP initiated clotting of plasma via the contact pathway. Ablation of intrinsic coagulation pathway proteases factor XII and factor XI protected mice from polyP-triggered lethal pulmonary embolism. Targeting polyP with phosphatases interfered with procoagulant activity of activated platelets and blocked platelet-induced thrombosis in mice. Addition of polyP restored defective plasma clotting of Hermansky-Pudlak Syndrome patients, who lack platelet polyP. The data identify polyP as a new class of mediator having fundamental roles in platelet-driven proinflammatory and procoagulant disorders. |
