Polyphosphate exerts differential effects on blood clotting, depending on polymer size
Polyphosphate exerts differential effects on blood clotting, depending on polymer size
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DOI：
10.1182/blood-2010-01-266791
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发表时间：
2010-11-18
期刊：
影响因子：
20.3
通讯作者：
Morrissey, James H.
中科院分区：
文献类型：
--
作者：
Smith, Stephanie A.;Choi, Sharon H.;Morrissey, James H.
聚磷酸盐是一种线性的无机磷酸盐聚合物，由活化的血小板分泌，并在许多感染性微生物中蓄积。我们最近发现，聚磷酸盐通过3个步骤调节凝血级联反应：它触发接触通路，它加速因子V的激活，它促进纤维蛋白聚合。我们现在报道，聚磷酸盐对血液凝固的影响是不同的，这取决于聚合物的长度。接触途径的最佳激活需要非常长的聚合物(~gt；=500mer，如微生物中的那些)，而较短的聚合物(~gt；=100mer，类似于血小板释放的聚合物长度)足以加速因子V的激活并消除组织因子途径抑制物的抗凝功能。聚磷酸盐对纤维蛋白凝块混浊度的最佳增强作用。焦磷酸盐也是由激活的血小板分泌的，它能有效地阻断聚磷酸盐介导的纤维蛋白凝块结构的增强，表明焦磷酸盐是一种新的纤维蛋白功能调节剂。总而言之，由血小板分泌的大小的聚磷酸盐在加速凝血反应方面非常有效，但在启动凝血反应或调节凝块结构方面效率较低。微生物聚磷酸盐是高度促凝剂，可能在宿主对病原体的反应中发挥作用。(血。2010；116(20)：4353-4359)
Polyphosphate, a linear polymer of inorganic phosphate, is secreted by activated platelets and accumulates in many infectious microorganisms. We recently showed that polyphosphate modulates the blood coagulation cascade at 3 steps: it triggers the contact pathway, it accelerates factor V activation, and it enhances fibrin polymerization. We now report that polyphosphate exerts differential effects on blood clotting, depending on polymer length. Very long polymers (>= 500mers, such as those present in microorganisms) were required for optimal activation of the contact pathway, while shorter polymers (>= 100mers, similar to the polymer lengths released by platelets) were sufficient to accelerate factor V activation and abrogate the anticoagulant function of the tissue factor pathway inhibitor. Optimal enhancement of fibrin clot turbidity by polyphosphate required >= 250mers. Pyrophosphate, which is also secreted by activated platelets, potently blocked polyphosphate-mediated enhancement of fibrin clot structure, suggesting that pyrophosphate is a novel regulator of fibrin function. In conclusion, polyphosphate of the size secreted by platelets is very efficient at accelerating blood clotting reactions but is less efficient at initiating them or at modulating clot structure. Microbial polyphosphate, which is highly procoagulant, may function in host responses to pathogens. (Blood. 2010;116(20):4353-4359)