Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis
Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis
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补体 5a 受体介导的中性粒细胞功能障碍与脓毒症的不良预后相关
DOI：
10.1038/cmi.2014.136
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发表时间：
2016-01-01
影响因子：
24.1
通讯作者：
Wang, Fu-Sheng
中科院分区：
文献类型：
--
作者：
Xu, Ruonan;Lin, Fang;Wang, Fu-Sheng
补体5a（C5 a）通过诱导中性粒细胞的功能损害而与脓毒症的发病机制有关;然而，C5 a受体（C5 aR; C5 aR和C5 L2）作为脓毒症管理的生物标志物的效用尚不确定。本研究探讨了中性粒细胞C5 aR和C5 L2的动态表达及其对中性粒细胞功能的影响。我们发现脓毒症患者中性粒细胞上C5 aR和C5 L2的表达水平低于健康和全身炎症反应综合征（SIRS）受试者，并且这种表达模式与疾病严重程度相关。此外，C5 aR和C5 L2的表达水平与脓毒症患者的生存相关。在体外，C5 a的加入显著降低了脓毒症患者中性粒细胞中C5 aR和C5 L2的表达水平和IL-8的产生。这些结果表明，C5 aRs的表达减少与中性粒细胞功能受损和脓毒症患者预后不良有关。总体而言，这些发现可能有助于建立C5 aRs表达水平作为早期标志物来预测脓毒症的严重程度。
Complement 5a (C5a) has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors (C5aRs; C5aR and C5L2) as biomarkers for the management of sepsis is uncertain. This study investigated the dynamic expression of C5aR and C5L2 on neutrophils and their effects on neutrophil function. We found that sepsis patients displayed low expression levels of C5aR and C5L2 on neutrophils compared to healthy and systemic inflammatory response syndrome (SIRS) subjects, and this expression pattern was correlated with disease severity. Additionally, the expression levels of C5aR and C5L2 were associated with the survival of sepsis patients. In vitro, the addition of C5a significantly reduced C5aR and C5L2 expression levels and IL-8 production in neutrophils from sepsis patients. Those findings suggest that the reduced expression of C5aRs was associated with the functional impairment of neutrophils and a poor prognosis for sepsis patients. Overall, these findings may help establish C5aRs expression levels as early markers to predict the severity of sepsis.