The Dynamics of Platelet Activation during the Progression of Streptococcal Sepsis

The Dynamics of Platelet Activation during the Progression of Streptococcal Sepsis
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DOI:
10.1371/journal.pone.0163531
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发表时间:
2016-09-22
期刊:
影响因子:
3.7
通讯作者:
Shannon, Oonagh
Shannon, Oonagh
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hurley, Sinead M.;Lutay, Nataliya;Shannon, Oonagh

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然而,血小板会导致炎症,但血小板活化在侵袭性细菌感染和脓毒症的病理生理反应过程中的作用尚不清楚。在此,我们研究了侵袭性化脓性链球菌感染小鼠模型在感染后 5、12 和 18 小时的血小板活化情况,并将其与感染参数相关联。离体血液样本中的血小板群显示整联蛋白激活或 CD62P 表面呈递没有增加,但血小板-中性粒细胞复合物形成和 CD62P 血浆水平在细菌传播和脓毒症进展过程中增加,表明体内发生了血小板激活。血小板-中性粒细胞复合物形成是血小板活化最具区别性的标志物。在脓毒症早期,血小板-中性粒细胞复合物增加至基线水平以上,但在脓毒症晚期,血小板-中性粒细胞复合物明显低于基线水平。从循环中去除这些复合物与器官损伤和肝窦中血小板积聚的显着增加同时发生,这表明循环中血小板的活化先于受损器官中血小板的积聚。结果表明,使用补充方法监测血小板活化可以在侵袭性化脓性链球菌感染的发病机制中提供预后信息。
Platelets contribute to inflammation however, the role of platelet activation during the pathophysiological response to invasive bacterial infection and sepsis is not clear. Herein, we have investigated platelet activation in a mouse model of invasive Streptococcus pyogenes infection at 5, 12, and 18 hours post infection and correlated this to parameters of infection. The platelet population in ex-vivo blood samples showed no increased integrin activation or surface presentation of CD62P, however platelet-neutrophil complex formation and plasma levels of CD62P were increased during bacterial dissemination and the progression of sepsis, indicating that platelet activation had occurred in vivo. Platelet-neutrophil complex formation was the most discriminatory marker of platelet activation. Platelet-neutrophil complexes were increased above baseline levels during early sepsis but decreased to significantly lower levels than baseline during late sepsis. The removal of these complexes from the circulation coincided with a significant increase in organ damage and the accumulation of platelets in the liver sinusoids, suggesting that platelet activation in the circulation precedes accumulation of platelets in damaged organs. The results demonstrate that monitoring platelet activation using complementary methods may provide prognostic information during the pathogenesis of invasive S. pyogenes infection.