Evidence for role of hydroxyl radical in complement and neutrophil-dependent tissue injury.
Evidence for role of hydroxyl radical in complement and neutrophil-dependent tissue injury.
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羟自由基在补体和中性粒细胞依赖性组织损伤中作用的证据。
DOI：
10.1172/jci111050
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Beauchamp,C
中科院分区：
文献类型：
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作者：
Ward,PA;Till,GO;Kunkel,R;Beauchamp,C
利用我们最近描述的眼镜蛇毒因子(CVF)全身激活补体后的大鼠急性肺损伤模型，我们证明了用人乳脱乳铁蛋白(其天然或衍生形式)而不是铁饱和乳铁蛋白对补体和中性粒细胞介导的肺损伤提供显著的保护作用。合成铁络合剂甲磺酸去铁胺也对肺损伤有保护作用。脱脂乳铁蛋白的保护作用与阻断CVF诱导的补体激活无关。我们还证明，离子铁的输注，特别是Fe3+，大大加强了全身补体激活后的肺血管损伤。最后，用羟基自由基(OH)的强效清除剂二甲基亚砜对动物进行预处理后，可以保护其免受肺损伤。在透射电子显微镜下，CVF处理的大鼠肺间质毛细血管内可见白细胞聚集和内皮细胞破坏，并伴有肺泡内出血和纤维蛋白沉积。在用载脂乳铁蛋白、甲磺酸去铁胺或二甲基亚砜保护的动物中，形态研究显示有白细胞聚集，但没有内皮细胞损伤、出血或纤维蛋白沉积。这些数据支持补体和中性粒细胞依赖的组织损伤可能与OH的产生有关的概念。从白血球激活后的过氧化氢中衍生出来的。图1图4图7图8
Using our recently described model of acute lung injury in rats after systemic activation of complement by cobra venom factor (CVF), we demonstrated that pretreatment of animals with human milk apolactoferrin (in its native or derivatized form), but not iron-saturated lactoferrin, provides significant protection against complement- and neutrophil-mediated lung injury. The synthetic iron chelator deferoxamine mesylate also affords protection from lung injury. The protective effects of apolactoferrin are not related to a blocking of CVF-induced complement activation. We also demonstrated that infusion of ionic iron, especially Fe3+, greatly potentiates lung vascular injury after systemic complement activation. Finally, protection from lung injury occurs in animals pretreated with the potent scavenger of hydroxyl radicals (OH.), dimethyl sulfoxide. Based on transmission electron microscopy, CVF-treated rats show leukoaggregates and endothelial cell destruction in interstitial pulmonary capillaries, along with intraalveolar hemorrhage and fibrin deposition. In animals protected with apolactoferrin, deferoxamine mesylate, or dimethyl sulfoxide, the morphological studies reveal leukoaggregates but no endothelial cell damage, hemorrhage, or fibrin deposition. These data support the concept that tissue injury that is complement and neutrophil dependent may be related to generation of OH. derived from H2O2 after leukocytic activation.ImagesFIGURE 1FIGURE 4FIGURE 7FIGURE 8