Synergistic enhancement of chemokine generation and lung injury by C5a or the membrane attack complex of complement
Synergistic enhancement of chemokine generation and lung injury by C5a or the membrane attack complex of complement
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DOI：
10.1016/s0002-9440(10)65405-3
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发表时间：
1999-05-01
影响因子：
6
通讯作者：
Ward, PA
中科院分区：
文献类型：
--
作者：
Czermak, BJ;Lentsch, AB;Ward, PA
补体在许多急性炎症反应中起重要作用。在当前的研究中，证明了在补体衍生的膜攻击复合物（MAC）的C5 a或亚裂解形式的存在下，用IgG免疫复合物共刺激的大鼠肺泡巨噬细胞表现出协同产生C-X-C（巨噬细胞炎性蛋白-2和龙氨酸诱导的中性粒细胞趋化因子）和C-C（巨噬细胞炎性蛋白-1 α和单核细胞趋化因子-1）趋化因子。在没有共刺激的情况下，C5 a或MAC不诱导趋化因子的产生。在体内研究中，单独的C5 a和MAC引起肺内产生有限的趋化因子或不产生趋化因子，但在共刺激物（IgG免疫复合物）存在下，C5 a和MAC引起C-X-C和C-C趋化因子的协同肺内产生，但不引起肿瘤坏死因子α的协同肺内产生。在这些条件下，中性粒细胞积聚增加，肺损伤也增加。这些观察结果表明，C5 a和MAC的功能协同与共刺激，以增强趋化因子的产生和强度的肺部炎症反应。
Complement plays an important role in many acute inflammatory responses. In the current studies it was demonstrated that, in the presence of either C5a or sublytic forms of the complement-derived membrane attack complex (MAC), rat alveolar macrophages costimulated with IgG immune complexes demonstrated synergistic production of C-X-C (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) and C-C (macrophage inflammatory protein-1 alpha and monocyte chemoattractant-l) chemokines. In the absence of the costimulus, C5a or MAC did not induce chemokine generation. In in vivo studies, C5a and MAC alone caused limited or no intrapulmonary generation of chemokines, but in the presence of a costimulus (IgG immune complexes) C5a and MAC caused synergistic intrapulmonary generation of C-X-C and C-C chemokines but not of tumor necrosis factor alpha. Under these conditions increased neutrophil accumulation occurred, as did lung injury. These observations suggest that C5a and MAC function synergistically with a costimulus to enhance chemokine generation and the intensity of the lung inflammatory response.