期刊
BLOOD
卷 129, 期 12, 页码 1707-1717出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2016-08-734988
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资金
- International Patient Organization for C1- Inhibitor Deficiencies
- Stichting Vrienden van Het UMC Utrecht
- Netherlands Organization for Scientific Research
- Hjart Lungfonden [20140741]
- Stockholms Lans Landsting [20140464]
- Vetenskapsradet [K2013-65X-21462-04-5]
- German Research Society [SFB877, TP A11, SFB841, TP B8]
- European Research Council grant [ERC-StG-2012-311575_F-12]
- National Institutes of Health (National Heart, Lung, and Blood Institute) [R01 HL101972]
- National Institutes of Health (National Institute of General Medical Sciences) [R01 GM116184]
- National Institutes of Health (American Heart Association) [13EIA12630000]
Polyphosphate is an inorganic polymer that can potentiate several interactions in the blood coagulation system. Blood platelets contain polyphosphate, and the secretion of platelet-derived polyphosphate has been associated with increased thrombus formation and activation of coagulation factor XII. However, the small polymer size of secreted platelet polyphosphate limits its capacity to activate factor XII in vitro. Thus, the mechanism by which platelet polyphosphate contributes to thrombus formation remains unclear. Using live-cell imaging, confocal and electron microscopy, we show that activated platelets retain polyphosphate on their cell surface. The apparent polymer size of membrane-associated polyphosphate largely exceeds that of secreted polyphosphate. Ultracentrifugation fractionation experiments revealed that membrane-associated platelet polyphosphate is condensed into insoluble spherical nanoparticles with divalent metal ions. In contrast to soluble polyphosphate, membrane-associated polyphosphate nanoparticles potently activate factor XII. Our findings identify membrane-associated polyphosphate in a nanoparticle state on the surface of activated platelets. We propose that these polyphosphate nanoparticles mechanistically link the procoagulant activity of platelets with the activation of coagulation factor XII.
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