Systemic complement activation, lung injury, and products of lipid peroxidation.
Systemic complement activation, lung injury, and products of lipid peroxidation.
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DOI：
10.1172/jci112001
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发表时间：
1985-08
期刊：
影响因子：
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通讯作者：
P. A. Ward;G. Till;J. Hatherill;T. M. Annesley;R. Kunkel
中科院分区：
文献类型：
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作者：
P. A. Ward;G. Till;J. Hatherill;T. M. Annesley;R. Kunkel
以前我们已经证明，静脉注射眼镜蛇毒因子(CVF)后，补体系统的全身激活会导致急性肺损伤，反映在肺血管通透性的增加以及肺血管内皮细胞损伤的形态学证据上。以肺血管通透性为参照，目前的研究表明，肺损伤与血浆中脂质过氧化产物(共轭双烯)的出现以及乳酸脱氢酶(LDH)及其同工酶(LDH-4)浓度的增加之间存在定量关系。注射CVF后，肺提取液中共轭双烯含量也升高，而肝、肾和脾提取液中未见升高。在注射CVF的大鼠中，没有证据表明肾脏或肝脏受到损害，这反映在没有出现蛋白尿，也没有检测到血清肝脏相关酶水平的升高。在注射CVF的大鼠血浆中发现的其他过氧化产物包括过氧化氢和具有席夫碱特征的荧光化合物。不足为奇的是，丙二醛没有被发现是氧自由基介导的肺血管损伤相关的脂质过氧化的可靠的血浆指标。在油酸诱导的氧自由基非依赖性肺损伤模型中，虽然在血浆中发现了大量的LDH和LDH-4，但没有检测到血浆共轭双烯水平的增加。在CVF注射的动物中，通过防止肺损伤的干预措施(中性粒细胞耗竭、过氧化氢酶、羟基自由基清除剂或铁络合剂)治疗后，共轭双烯、过氧化氢和荧光产物的血浆水平显著降低。肺切片的形态计量学分析表明，保护性干预措施不干扰补体系统激活后中性粒细胞在肺间质毛细血管中的聚集。在佛波醇刺激的中性粒细胞的体外研究中，未能证明共轭双烯的出现，这表明注射CVF的动物血浆中出现的双烯不是中性粒细胞自毒变化的结果。本文提供的数据表明，通过血浆中脂质过氧化产物的出现，可以监测吞噬细胞产生的氧自由基所介导的急性肺损伤。
Previously we have demonstrated that systemic activation of the complement system after intravenous injection of cobra venom factor (CVF) results in acute lung injury as reflected by increases in the vascular permeability of the lung as well as by morphologic evidence of damage to lung vascular endothelial cells. In using the vascular permeability of the lung as the reference, the current studies show a quantitative correlation between lung injury and the appearance in plasma of lipid peroxidation products (conjugated dienes) as well as increased concentrations of lactic dehydrogenase (LDH) and one of its isoenzymes (LDH-4). After injection of CVF, extracts of lungs also showed elevated levels of conjugated dienes, whereas no elevations were found in extracts of liver, kidney, and spleen. There was no evidence in CVF-injected rats of renal or hepatic injury as reflected by the lack of development of proteinuria and the failure to detect increased serum levels of liver-related enzymes. Other peroxidation products identified in plasma of CVF-injected rats involved hydroperoxides and fluorescent compounds with features of Schiff bases. Not surprisingly, malondialdehyde was not found to be a reliable plasma indicator of lipid peroxidation associated with oxygen radical-mediated lung vascular injury. In using a model of oxygen radical-independent lung injury induced by oleic acid, although large amounts of LDH and LDH-4 were found in the plasma, no increases in plasma levels of conjugated dienes were detected. In CVF-injected animals treated with interventions protective against lung injury (neutrophil depletion, catalase, hydroxyl radical scavengers, or iron chelators), there were striking reductions in the plasma levels of conjugated dienes, hydroperoxides, and fluorochromic products. Morphometric analysis of lung sections revealed that the protective interventions did not interfere with the accumulation of neutrophils in lung interstitial capillaries after systemic activation of complement. In vitro studies with phorbol-stimulated neutrophils failed to demonstrate appearance of conjugated dienes, suggesting that the dienes appearing in plasma of CVF-injected animals are not the result of autotoxic changes in neutrophils. The data presented in this paper suggest that acute lung injury mediated by oxygen radicals derived from phagocytic cells can be monitored by the appearance in plasma of products of lipid peroxidation.