Impaired mast cell-dependent natural immunity in complement C3-deficient mice
Impaired mast cell-dependent natural immunity in complement C3-deficient mice
复制标题
DOI：
10.1038/36586
复制
发表时间：
1997-11-13
期刊：
影响因子：
64.8
通讯作者：
Carroll, MC
中科院分区：
文献类型：
--
作者：
Prodeus, AP;Zhou, XN;Carroll, MC
补体系统被广泛认为是正常炎症所必需的，尤其是因为它有能力激活肥大细胞(1-5)。然而，最近的研究质疑补体在几个肥大细胞依赖的炎症反应中的重要性(6-9)。为了研究补体在肥大细胞依赖的自然免疫中的作用，我们检测了补体缺乏小鼠(10，11)对盲肠结扎和穿孔(12)，依赖肥大细胞的急性化脓性腹膜炎模型(12，13)和肿瘤坏死因子-α(TNF-α)的反应。我们发现C4或C3缺陷小鼠(10，11)‘’对盲肠结扎和穿孔比野生型(WT)对照组更敏感(24小时死亡率分别为100%和20%)。C3缺乏的小鼠在腹膜肥大细胞脱颗粒、产生肿瘤坏死因子-α、中性粒细胞渗透和细菌清除方面也表现出减少。用纯化的C3蛋白处理C3缺陷小鼠，可增强小鼠腹膜肥大细胞的活化、产生肿瘤坏死因子-α、中性粒细胞募集、细菌吞噬功能和对盲肠结扎和穿孔的抵抗力，证实缺陷是补体依赖的。这些结果提供了正式的证据，即补体激活对于充分表达这种肥大细胞依赖的细菌感染模型的先天免疫是必不可少的。
The complement system is widely regarded as essential for normal inflammation, not least because of its ability to activate mast cells(1-5). However, recent studies have called into question the importance of complement in several examples of mast cell-dependent inflammatory responses(6-9). To investigate the role of complement in mast cell-dependent natural immunity, we examined the responses of complement-deficient mice(10,11) to caecal ligation and puncture(12), model of acute septic peritonitis(12,13) that is dependent on mast cells and tumour necrosis factor-alpha (TNF-alpha). We found that C4- or C3-deficient mice(10,11) '' were much more sensitive to caecal ligation and puncture than wild-type (WT) controls (100% versus 20% in 24-h mortality, respectively). C3-deficient mice also exhibited reductions in peritoneal mast cell degranulation, production of TNF-alpha, neutrophil infiltration and clearance of bacteria. Treating the C3-deficient mice with purified C3 protein enhanced activation of peritoneal mast cells, TNF-alpha production, neutrophil recruitment, opsonophagocytosis of bacteria and resistance to caecal ligation and puncture, confirming that the defects were complement-dependent. These results provide formal evidence that complement activation is essential for the full expression of innate immunity in this mast cell-dependent model of bacterial infection.