Regulation by C5a of neutrophil activation during sepsis
Regulation by C5a of neutrophil activation during sepsis
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DOI：
10.1016/s1074-7613(03)00206-1
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发表时间：
2003-08-01
期刊：
影响因子：
32.4
通讯作者：
Ward, PA
中科院分区：
文献类型：
--
作者：
Riedemann, NC;Guo, RF;Ward, PA
在脓毒症中，有证据表明过量的C5a产生导致先天免疫功能受损，与预后不良有关。我们现在报道，体外中性粒细胞暴露于C5a会导致IkappaBalpha水平升高，tnf - kappab依赖性基因转录减少，脂多糖（LPS）诱导的tnf - falpha产生减少。盲肠结扎/穿刺（CLP）诱导的脓毒症大鼠的中性粒细胞也得到了类似的结果。这种变化被抗体诱导的体内阻断C5a逆转。相比之下，肺泡巨噬细胞体外暴露于C5a和LPS导致TNFalpha的产生增加，而IkappaBalpha没有增加。这些数据表明，clp诱导的脓毒症导致c5a依赖性中性粒细胞功能障碍，其特征是与NF-kappaB激活相关的信号改变。
In sepsis, there is evidence that excessive C5a generation leads to compromised innate immune functions, being associated with poor outcome. We now report that in vitro exposure of neutrophils to C5a causes increased levels Of IkappaBalpha, decreased NF-kappaB-dependent gene transcription of TNFalpha, and decreased lipopolysaccharide (LPS)-induced TNFalpha production. Similar findings were obtained with neutrophils from cecal ligation/puncture (CLP)-induced septic rats. Such changes were reversed by antibody-induced in vivo blockade of C5a. In contrast, in vitro exposure of alveolar macrophages to C5a and LPS resulted in enhanced production of TNFalpha and no increase in IkappaBalpha. These data suggest that CLP-induced sepsis causes a C5a-dependent dysfunction of neutrophils, which is characterized by altered signaling associated with NF-kappaB activation.