Role of C5a in multiorgan failure during sepsis
Role of C5a in multiorgan failure during sepsis
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DOI：
10.4049/jimmunol.166.2.1193
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发表时间：
2001-01-15
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, VJ;Ward, PA
在患有脓毒症的人类中，多器官衰竭（MOF）的发作，特别是涉及肝脏、肺和肾脏，是与高死亡率相关的众所周知的并发症。我们以前的研究与盲肠结扎/穿孔（CLP）模型的脓毒症在大鼠中揭示了C5 a诱导的缺陷，在呼吸爆发的中性粒细胞。在目前的CLP研究中，MOF发生在前48小时内，并出现肝功能障碍和肺功能障碍（动脉O-2分压下降，CO2分压升高）。在该模型中，出现了早期呼吸性酸中毒，随后出现代谢性酸中毒，血乳酸水平升高。在这些事件中，血液中性粒细胞失去了对C5 a和细菌趋化因子fMLP的趋化反应。神经功能障碍与C5 a结合几乎完全丧失相关，但fMLP结合保持正常。如果CLP动物用抗C5 a治疗，则MOF和乳酸酸中毒的指标大大减弱。在相同条件下，C5 a与血液中性粒细胞的结合保持完整;串联，保留了对C5 a和fMLP的体外趋化反应。这些数据表明，在CLP脓毒症模型中，抗C5 a治疗可预防MOF的发展和伴随的血液中性粒细胞功能障碍的发作。这可以解释抗C5 a在CLP脓毒症模型中的保护作用。
In humans with sepsis, the onset of multiorgan failure (MOF), especially involving liver, lungs, and kidneys, is a well known complication that is associated with a high mortality rate. Our previous studies with the cecal ligation/puncture (CLP) model of sepsis in rats have revealed a C5a-induced defect in the respiratory burst of neutrophils. In the current CLP studies, MOF occurred during the first 48 h with development of liver dysfunction and pulmonary dysfunction (falling arterial partial pressure of O-2, rising partial pressure of CO2). In this model an early respiratory alkalosis developed, followed by a metabolic acidosis with increased levels of blood lactate. During these events, blood neutrophils lost their chemotactic responsiveness both to C5a and to the bacterial chemotaxin, fMLP. Neutrophil dysfunction was associated with virtually complete loss in binding of C5a, but binding of fMLP remained normal. If CLP animals were treated with anti-C5a, indicators of MOF and lactate acidosis were greatly attenuated. Under the same conditions, C5a binding to blood neutrophils remained intact; in tandem, in vitro chemotactic responses to C5a and fMLP were retained. These data suggest that, in the CLP model of sepsis, treatment with anti-C5a prevents development of MOF and the accompanying onset of blood neutrophil dysfunction. This may explain the protective effects of anti-C5a in the CLP model of sepsis.