Changes in the novel orphan, C5a receptor (C5L2), during experimental sepsis and sepsis in humans
Changes in the novel orphan, C5a receptor (C5L2), during experimental sepsis and sepsis in humans
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DOI：
10.4049/jimmunol.174.2.1104
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发表时间：
2005-01-15
影响因子：
4.4
通讯作者：
Ward, PA
中科院分区：
文献类型：
--
作者：
Huber-Lang, M;Sarma, JV;Ward, PA
脓毒症与广泛的补体激活有关，损害先天免疫防御，特别是在中性粒细胞（PMN）中。最近，在PMN上检测到第二种C5 a受体（C5 L2），但没有细胞内信号传导的证据。本研究旨在确定脓毒症期间血液PMN中C5 L2的变化。在体外暴露的PMN C5 a，但不fMLP，导致C5 L2的含量减少。盲肠结扎和穿孔诱导的脓毒症大鼠后，PMN表现出C5 L2的时间依赖性下降。在实验性脓毒症期间C5 a的体内阻断导致C5 L2的保存。同样，进行性脓毒症患者的PMN显示C5 L2表达显著降低（n = 26），这在发生多器官衰竭的患者中几乎被消除（n = 10）。相比之下，脓毒症幸存者表现出C5 L2的保留（n = 12/13）。这些数据表明，C5 L2对中性粒细胞减少脓毒症期间由于全身产生的C5 a，这是与预后不良。
Sepsis is associated with extensive complement activation, compromising innate immune defenses, especially in neutrophils (PMN). Recently, a second C5a receptor (C5L2) was detected on PMN without evidence of intracellular signaling. The current study was designed to determine changes in C5L2 in blood PMN during sepsis. In vitro exposure of PMN to C5a, but not to fMLP, led to reduced content of C5L2. Following cecal ligation and puncture-induced sepsis in rats, PMN demonstrated a time-dependent decrease in C5L2. In vivo blockade of C5a during experimental sepsis resulted in preservation of C5L2. Similarly, PMN from patients with progressive sepsis showed significantly reduced C5L2 expression (n = 26), which was virtually abolished in patients who developed multiorgan failure (n = 10). In contrast, sepsis survivors exhibited retention of C5L2 (n = 12/13). The data suggest that C5L2 on PMN diminishes during sepsis due to systemic generation of C5a, which is associated with a poor prognosis.