Quezado Z M, Hoffman W D, Winkelstein J A, Yatsiv I, Koev C A, Cork L C, Elin R J, Eichacker P Q, Natanson C
Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1994 Feb 1;179(2):569-78. doi: 10.1084/jem.179.2.569.
We investigated whether the third component of complement (C3) is involved in the pathophysiology of endotoxic shock, and if it is involved, whether it plays a protective role or whether it mediates shock and multiple organ failure. In a prospective, controlled investigation, six Brittany spaniels that were homozygous for a genetically determined deficiency of C3 (C3 deficient, < 0.003% of normal serum C3 levels) and six heterozygous littermates (controls, approximately 50% of mean normal serum C3 level) were given 2 mg/kg of reconstituted Escherichia coli 026:B6 acetone powder as a source of endotoxin, intravenously. All animals were given similar fluid and prophylactic antibiotic therapy, and had serial hemodynamic variables obtained. After E. coli endotoxin infusion, C3-deficient animals had higher peak levels of endotoxin and less of a rise in temperature than controls (P < 0.05). During the first 4 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean central venous pressure and mean pulmonary artery pressure than controls (P < 0.02). During the first 48 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean arterial pH, left ventricular ejection fraction, and mean pulmonary capillary wedge pressure, and greater increases in mean arterial lactate, arterial-alveolar O2 gradient, and transaminases (aspartate aminotransferase and alanine aminotransferase) than controls, (all P < 0.05). After E. coli endotoxin infusion, C3-deficient animals compared to controls had significantly less of a decrease in mean C5 levels (P < 0.01), but similar (P = NS) increases in circulating tumor necrosis factor levels, bronchoalveolar lavage neutrophils, and protein, and similar (P = NS) decreases in blood leukocytes and platelets. Two of six C3-deficient animals and two of six controls died. In summary, after intravenous infusion of E. coli endotoxin, canines with C3 deficiency have decreased endotoxin clearance and worse E. coli endotoxin-induced shock and organ damage. Thus, the third component of the complement system plays a beneficial role in the host defense against E. coli endotoxic shock.
我们研究了补体第三成分（C3）是否参与内毒素休克的病理生理学过程，如果参与，它是发挥保护作用还是介导休克和多器官功能衰竭。在一项前瞻性对照研究中，给6只因基因决定而C3缺乏的纯合布列塔尼猎犬（C3缺乏，血清C3水平低于正常血清C3水平的0.003%）和6只杂合同窝犬（对照组，血清C3水平约为正常血清平均水平的50%）静脉注射2mg/kg重组大肠杆菌026:B6丙酮粉末作为内毒素来源。所有动物均接受相似的液体和预防性抗生素治疗，并记录连续的血流动力学变量。注入大肠杆菌内毒素后，C3缺乏的动物内毒素峰值水平高于对照组，体温升高幅度小于对照组（P<0.05）。在注入大肠杆菌内毒素后的最初4小时内，C3缺乏的动物平均中心静脉压和平均肺动脉压的下降幅度显著大于对照组（P<0.02）。在注入大肠杆菌内毒素后的最初48小时内，C3缺乏的动物平均动脉pH值、左心室射血分数和平均肺毛细血管楔压的下降幅度显著大于对照组，平均动脉乳酸、动脉-肺泡氧梯度和转氨酶（天冬氨酸转氨酶和丙氨酸转氨酶）的升高幅度也大于对照组（所有P<0.05）。注入大肠杆菌内毒素后，与对照组相比，C3缺乏的动物平均C5水平下降幅度显著较小（P<0.01），但循环肿瘤坏死因子水平、支气管肺泡灌洗中性粒细胞和蛋白质的升高幅度相似（P=无显著性差异），血液白细胞和血小板的下降幅度也相似（P=无显著性差异）。6只C3缺乏的动物中有2只死亡，6只对照组动物中有2只死亡。总之，静脉注射大肠杆菌内毒素后，C3缺乏的犬内毒素清除能力下降，大肠杆菌内毒素诱导的休克和器官损伤更严重。因此，补体系统的第三成分在宿主抵御大肠杆菌内毒素休克中发挥有益作用。
