THE 3RD COMPONENT OF COMPLEMENT PROTECTS AGAINST ESCHERICHIA-COLI ENDOTOXIN-INDUCED SHOCK AND MULTIPLE ORGAN FAILURE
THE 3RD COMPONENT OF COMPLEMENT PROTECTS AGAINST ESCHERICHIA-COLI ENDOTOXIN-INDUCED SHOCK AND MULTIPLE ORGAN FAILURE
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DOI：
10.1084/jem.179.2.569
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发表时间：
1994-02-01
影响因子：
15.3
通讯作者：
NATANSON, C
中科院分区：
文献类型：
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作者：
QUEZADO, ZMN;HOFFMAN, WD;NATANSON, C
我们研究了补体的第三组分（C3）是否参与内毒素休克的病理生理学，如果参与，它是否起保护作用或是否介导休克和多器官衰竭。在一项前瞻性对照研究中，对6只遗传确定的C3缺乏纯合子（C3缺乏，<正常血清C3水平的0.003%）的布列塔尼犬和6只杂合子同窝犬（对照，约为平均正常血清C3水平的50%）静脉给予2 mg/kg的重组大肠杆菌026：B6丙酮粉作为内毒素来源。所有动物均给予相似的液体和预防性抗生素治疗，并获得了一系列血流动力学变量。在E.大肠杆菌内毒素输注后，CS缺陷组动物内毒素峰值水平高于对照组，体温升高幅度低于对照组（P < 0.05）。在E. C3缺乏组的平均中心静脉压和平均肺动脉压均较对照组显著降低（P < 0.02）。在E.与对照组相比，C3缺乏组动物的平均动脉pH、左心室射血分数和平均肺毛细血管楔压显著降低，平均动脉乳酸、动脉-肺泡氧分压差和转氨酶（天冬氨酸转氨酶和丙氨酸转氨酶）显著升高（均P < 0.05）。在E.与对照组相比，C3缺陷动物的平均C5水平下降显著较少（P < 0.01），但循环肿瘤坏死因子水平、支气管肺泡灌洗液中性粒细胞和蛋白质增加相似（P = NS），血液白细胞和血小板减少相似（P = NS）。6只C3缺陷动物中的2只和6只对照动物中的2只死亡。综上所述，静脉滴注E. C3缺乏犬内毒素清除率降低，E.大肠杆菌内毒素引起的休克和器官损伤。因此，补体系统的第三组分在宿主防御E.大肠杆菌内毒素休克。
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, approximate to 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, CS-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 O-2 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.