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Cited by 831

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Platelet Polyphosphates Are Proinflammatory and Procoagulant Mediators In Vivo

Open access
Müller, Felicitas, Mutch, Nicola J., Schenk, Wolfdieter A., Smith, Stephanie A., Esterl, Lucie, Spronk, Henri M., Schmidbauer, Stefan, Gahl, William A., Morrissey, James H., Renné, Thomas·2009·Cell
DOI 10.1016/j.cell.2009.11.001
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Abstract

Summary 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. Infusion of polyP restored defective plasma clotting of Hermansky-Pudlak Syndrome patients, which lack platelet polyP. The data identify polyP as a new class of mediator having fundamental roles in platelet-driven proinflammatory and procoagulant disorders.

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Metadata

Authors
Müller, F., Mutch, N. J., Schenk, W. A., Smith, S. A., Esterl, L., Spronk, H. M., Schmidbauer, S., Gahl, W. A., Morrissey, J. H., & Renné, T.
Venue
Cell
Publisher
Elsevier BV
Published
2009-12
Volume
139
Issue
6
Pages
1143-1156
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2009.11.001
OpenAlex
W2083884362
Cited by
831
References
1
FWCI
25.75
Type
journal article
Language
en
Open access
bronze

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