Protection of innate immunity by C5aR antagonist in septic mice
Protection of innate immunity by C5aR antagonist in septic mice
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DOI：
10.1096/fj.02-0209com
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发表时间：
2002-10-01
期刊：
影响因子：
4.8
通讯作者：
Ward, PA
中科院分区：
文献类型：
--
作者：
Huber-Lang, MS;Riedeman, NC;Ward, PA
已知先天免疫功能在脓毒症期间受损，通常具有致命的后果。在大鼠中也有证据表明，脓毒症与过度的补体激活和强效过敏毒素C5 a的产生有关。在C5 a受体（C5 aR）的环肽拮抗剂（C5 aRa）存在下，鼠I-125-C5 a与鼠中性粒细胞的结合减少，小鼠中性粒细胞对小鼠C5 a的体外趋化反应显著减弱，暴露于C5 a的中性粒细胞产生过氧化氢（H2 O2）的获得性缺陷被逆转，肺内沉积IgG免疫复合物后，小鼠肺通透性指数（白蛋白的血管外渗漏）显著降低。在盲肠结扎/穿孔（CLP）后发展脓毒症并用C5 aRa治疗的小鼠的存活率大大提高。这些数据表明，C5 aRa干扰中性粒细胞对C5 a的反应，防止脓毒症期间C5 a诱导的先天免疫损害，大大提高了CLP后的存活率。
Innate immune functions are known to be compromised during sepsis, often with lethal consequences. There is also evidence in rats that sepsis is associated with excessive complement activation and generation of the potent anaphylatoxin C5a. In the presence of a cyclic peptide antagonist (C5aRa) to the C5a receptor (C5aR), the binding of murine I-125-C5a to murine neutrophils was reduced, the in vitro chemotactic responses of mouse neutrophils to mouse C5a were markedly diminished, the acquired defect in hydrogen peroxide (H2O2) production of C5a-exposed neutrophils was reversed, and the lung permeability index (extravascular leakage of albumin) in mice after intrapulmonary deposition of IgG immune complexes was markedly diminished. Mice that developed sepsis after cecal ligation/puncture (CLP) and were treated with C5aRa had greatly improved survival rates. These data suggest that C5aRa interferes with neutrophil responses to C5a, preventing C5a-induced compromise of innate immunity during sepsis, with greatly improved survival rates after CLP.