Prodeus A P, Zhou X, Maurer M, Galli S J, Carroll M C
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature. 1997 Nov 13;390(6656):172-5. doi: 10.1038/36586.
The complement system is widely regarded as essential for normal inflammation, not least because of its ability to activate mast cells. However, recent studies have called into question the importance of complement in several examples of mast cell-dependent inflammatory responses. To investigate the role of complement in mast cell-dependent natural immunity, we examined the responses of complement-deficient mice to caecal ligation and puncture, a model of acute septic peritonitis that is dependent on mast cells and tumour necrosis factor-alpha (TNF-alpha). We found that C4- or C3-deficient mice 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.
补体系统被广泛认为对正常炎症至关重要，这尤其是因为它具有激活肥大细胞的能力。然而，最近的研究对补体在几种肥大细胞依赖性炎症反应中的重要性提出了质疑。为了研究补体在肥大细胞依赖性天然免疫中的作用，我们检测了补体缺陷小鼠对盲肠结扎和穿刺的反应，这是一种依赖肥大细胞和肿瘤坏死因子-α（TNF-α）的急性脓毒症性腹膜炎模型。我们发现，C4缺陷或C3缺陷小鼠对盲肠结扎和穿刺的敏感性远高于野生型（WT）对照（24小时死亡率分别为100%和20%）。C3缺陷小鼠还表现出腹膜肥大细胞脱颗粒减少、TNF-α产生减少、中性粒细胞浸润减少以及细菌清除减少。用纯化的C3蛋白治疗C3缺陷小鼠可增强腹膜肥大细胞的激活、TNF-α的产生、中性粒细胞募集、细菌的调理吞噬作用以及对盲肠结扎和穿刺的抵抗力，证实这些缺陷是补体依赖性的。这些结果提供了正式证据，表明在这种肥大细胞依赖性细菌感染模型中，补体激活对于先天免疫的充分表达至关重要。
