Complement and neutrophil activation during cardiopulmonary bypass: a study in the complement-deficient dog.
Complement and neutrophil activation during cardiopulmonary bypass: a study in the complement-deficient dog.
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体外循环期间的补体和中性粒细胞激活：针对补体缺陷狗的研究。
DOI：
10.1016/0003-4975(94)90995-4
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Cameron,DE
中科院分区：
文献类型：
--
作者：
Gillinov,AM;Redmond,JM;Winkelstein,JA;Zehr,KJ;Herskowitz,A;Baumgartner,WA;Cameron,DE
已知心脏搭桥术（CPB）会引起补体和中性粒细胞活化，但这些组分在CPB诱导的炎症中的相对重要性和相互作用尚不清楚。在这项研究中，一个品系的狗在补体第三成分（C3）的遗传缺陷，用于确定C3的贡献neutropnil激活和肺损伤后CPB。11只犬（5只C3缺陷犬和6只对照犬）接受了150分钟的低温CPB（28 °C），随后观察2小时。CPB前，对照组C3水平正常，C3缺乏犬低于正常值的1%。在对照犬中，CPB 1小时后C3的功能活性下降至基线的53.2%，CPB后肺中存在C3沉积的免疫组化证据; C3缺陷犬肺中无C3沉积。尽管两组在CPB期间发生了相似程度的中性粒细胞减少，但在CPB 1小时后，C3缺陷犬的中性粒细胞粘附分子亚单位CD 18的表达显著低于对照组（45.9 ± 3.7对82.9 ± 10.0平均荧光单位;p< 0.02）。转流后肺组织髓过氧化物酶含量在C3缺乏犬中也较低（43.8 ± 4.6对71.1 ± 8.6 μmol · 10 mg−1· min−1;p< 0.03）。心脏搭桥术相关的肺损伤（通过肺泡-动脉氧分压差、肺血管阻力、肺水百分比以及光镜和电镜观察评估）在组间相似。这些结果表明：（1）C3在CPB期间沉积在肺血管内皮上;（12）C3介导CPB后肺中性粒细胞CD 18表达增加和中性粒细胞隔离。此外，这些结果表明，补体激活的调制是一种潜在的手段，以减少中性粒细胞活化在CPB期间，但预防与CPB相关的器官损伤将需要抑制多臂的炎症级联反应。
Cardiopulmonary bypass (CPB) is known to cause complement and neutrophil activation, but the relative importance and interaction of these components in CPB-induced inflammation is unknown. In this study, a strain of dogs genetically deficient in the third component of complement (C3) was used to determine the contribution of C3 to neutropnil activation and pulmonary injury after CPB. Eleven dogs (5 C3-deficient and 6 controls) underwent 150 minutes of hypothermic CPB (28 °C) followed by 2 hours of observation. Before CPB, C3 levels were normal in controls and less than 1% of normal in C3-deficient dogs. In control dogs, functional activity of C3 decreased to 53.2% of baseline after 1 hour of CPB and there was immunohistochemical evidence of C3 deposition in lung after CPB; C3-deficient dogs had no C3 deposition in lung. Although similar degrees of neutropenia occurred during CPB in the two groups, expression of neutrophil adhesion molecule subunit CD18 was significantly lower in C3-deficient dogs than controls after 1 hour of CPB (45.9 ± 3.7 versus 82.9 ± 10.0 mean fluorescence units;p< 0.02). Postbypass lung tissue myeloperoxidase content was also less in C3-deficient dogs (43.8 ± 4.6 versus 71.1 ± 8.6 μmol · 10 mg−1· min−1;p< 0.03). Cardiopulmonary bypass-associated lung injury (assessed by alveolar-arterial oxygen gradient, pulmonary vascular resistance, percent lung water, and light and electron microscopic appearance) was similar between groups. These results demonstrate that (1) C3 is deposited on pulmonary vascular endothelium during CPB and 12) C3 mediates increased expression of neutrophil CD18 and neutrophil sequestration in lung after CPB. Furthermore, these results suggest that modulation of complement activation is a potential means to reduce neutrophil activation during CPB, but that prevention of much of the organ injury associated with CPB will require inhibition of multiple arms of the inflammatory cascade.