INCREASED OXIDATION OF EXTRACELLULAR GLUTATHIONE BY BRONCHOALVEOLAR INFLAMMATORY CELLS IN DIFFUSE FIBROSING ALVEOLITIS
INCREASED OXIDATION OF EXTRACELLULAR GLUTATHIONE BY BRONCHOALVEOLAR INFLAMMATORY CELLS IN DIFFUSE FIBROSING ALVEOLITIS
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DOI：
10.1183/09031936.95.08081286
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发表时间：
1995-08-01
影响因子：
24.3
通讯作者：
FRUHMANN, G
中科院分区：
文献类型：
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作者：
BEHR, J;DEGENKOLB, B;FRUHMANN, G
不平衡的氧化应激被认为是弥漫性纤维化肺泡炎（DFA）发病的一个重要因素，本研究的目的是探讨从培养的支气管肺泡炎细胞（ba -细胞）释放的活性氧代谢物（ROMs）在谷胱甘肽氧化中的作用，我们研究了10名健康对照者和20名弥漫性纤维化肺泡炎患者（均为非吸烟者）的支气管肺泡灌洗液样本。通过支气管肺泡灌洗（BAL）获得的ba细胞与50 μ M的还原型谷胱甘肽（GSH）孵育，检测ba细胞衍生的氧化剂将GSH氧化为谷胱甘肽二硫（GSSG），上清液中GSH下降。测定上皮衬里液（ELF）中总谷胱甘肽（gshtt = GSH + 2 GSSG）和GSSG，以及BAL蛋白中蛋氨酸亚砜（Met(O)）的含量。弥漫性纤维化肺泡炎中ba -细胞的氧化活性增强，gsht和GSH降低，GSSG:GSH比值升高，ba -细胞的氧化活性与GSSG:GSH比值呈正相关，与蛋氨酸亚砜含量不相关，蛋氨酸亚砜含量在弥漫性纤维化肺泡炎中升高，与gsht呈负相关。蛋氨酸硫化物含量也与BAL中性粒细胞百分比呈正相关。我们得出结论，ba细胞衍生的活性氧能够在体外氧化细胞外GSH，体外ba细胞的氧化活性与ELF中GSSG:GSH的比值正相关，表明体内对细胞外GSH的氧化作用也可能发生，因此，ba细胞释放的活性氧代谢物可能有助于降低抗氧化筛选，从而引起其他分子的氧化损伤。从硫代蛋氨酸含量的增加可以看出。
An unbalanced oxidative stress is thought to be an important element in the pathogenesis of diffuse fibrosing alveolitis (DFA), The purpose of our study was to investigate the role of reactive oxygen metabolites (ROMs) released from cultured bronchoalveolar inflammatory cells (BA-cells) on glutathione oxidation, We studied bronchoalveolar lavage samples from 10 healthy controls and from 20 patients with diffuse fibrosing alveolitis (all were nonsmokers).BA-cells obtained by bronchoalveolar lavage (BAL) were incubated with 50 mu M of reduced glutathione (GSH), Oxidation of GSH to glutathione disulphide (GSSG) by BA-cell derived oxidants was detected as a decline of GSH in the supernatants. Total glutathione (GSHtot = GSH + 2 GSSG) and GSSG in the epithelial lining fluid (ELF), and methionine sulphoxide (Met(O)) content of BAL proteins were determined.In diffuse fibrosing alveolitis the oxidative activity of BA-cells was enhanced, GSHtot and GSH were decreased, whereas the GSSG:GSH ratio was increased, The oxidative activity of BA-cells correlated positively with the GSSG:GSH ratio, but not with the methionine sulphoxide content, The methionine sulphoxide content was elevated in diffuse fibrosing alveolitis and inversely correlated with GSHtot. The methionine sulphoxide content also correlated positively with the percentage of BAL neutrophils.We conclude that BA-cell-derived reactive oxygen species are capable of oxidizing extracellular GSH in vitro, The positive correlation between the BA-cell oxidative activity in vitro and GSSG:GSH ratio in ELF suggests that a similar oxidative effect on extracellular GSH may also occur in vivo, Thus, reactive oxygen metabolites released from BA-cells may contribute to a lowered antioxidant screen, thereby causing oxidative damage of other molecules, as indicated by an increase of methionine sulphoxide content.