Effect of chronic ethanol ingestion on alveolar type II cell: Glutathione and inflammatory mediator-induced apoptosis
Effect of chronic ethanol ingestion on alveolar type II cell: Glutathione and inflammatory mediator-induced apoptosis
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DOI：
10.1111/j.1530-0277.2001.tb02320.x
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发表时间：
2001-07-01
影响因子：
3.2
通讯作者：
Guidot, DM
中科院分区：
文献类型：
--
作者：
Brown, LAS;Harris, FL;Guidot, DM
背景：在脓毒症患者中，慢性酒精滥用增加了急性呼吸窘迫综合征的发生率，该综合征需要肺泡II型细胞的增殖和分化来修复受损的肺泡上皮。我们之前在一个大鼠模型中表明，长期摄入乙醇会降低II型细胞中抗氧化剂谷胱甘肽(GSH)的含量，并加剧内毒素介导的急性肺损伤。我们推测这种由乙醇引起的GSH耗竭，特别是线粒体GSH，使II型细胞容易受到炎性介质诱导的细胞凋亡。然后分离肺泡II型细胞，用过氧化氢或肿瘤坏死因子-α处理。测定对谷胱甘肽(胞浆和线粒体)、细胞凋亡事件和坏死的影响。结果：慢性酒精摄入可导致线粒体GSH进行性降低，基础细胞凋亡率和坏死率进行性升高(p<0.05)。此外，细胞对过氧化氢或肿瘤坏死因子-α诱导的细胞色素c释放、半胱氨酸天冬氨酸蛋白酶3的激活、凋亡和坏死的敏感性逐渐增加(p<0.05)。结论：慢性酒精摄入可导致线粒体GSH逐渐耗竭，并使II型细胞对炎性介质诱导的细胞凋亡和坏死敏感。当这些细胞的增殖和分化对受损的肺泡上皮的修复至关重要时，这些效应可能在急性应激期间特别相关，并可能对有酒精史的患者的急性呼吸窘迫综合征的治疗产生重要的影响。虐待。
Background: In septic patients, chronic alcohol abuse increases the incidence of the acute respiratory distress syndrome, a syndrome that requires alveolar type II cellproliferation and differentiation for repair of the damaged alveolar epithelium. We previously showed in a rat model that chronic ethanol ingestion decreased the antioxidant glutathione (GSH) in type II cells and exacerbated endotoxin-mediated acute lung injury. We hypothesized that this GSH depletion by ethanol, particularly mitochondrial GSH, predisposed type II cells to inflammatory mediator-induced apoptosis.Methods: Adult male rats were fed the Lieber-DeCarli diet for 2, 6, or 16 weeks. Alveolar type II cells were then isolated and treated with hydrogen peroxide or TNF-alpha. The effect on glutathione (cytosolic and mitochondrial), apoptotic events, and necrosis were determined. in other studies, rats were fed ethanol for 6 weeks and were treated with endotoxin and apoptosis of type II cells determined by the TUNEL method.Results: Chronic ethanol ingestion alone resulted in a progressive decrease in mitochondrial GSH and a progressive increase in the basal apoptosis and necrosis rate (p less than or equal to 0.05). Furthermore; there was a progressive increase in the sensitivity of the cells to H2O2 or TNF-alpha induced cytochrome c release, caspase 3 activation, apoptosis, and necrosis (p less than or equal to 0.05). Finally, there was a 2-fold increase in apoptotic type II cells in vivo when chronic ethanol ingestion was superimposed on endotoxemia.Conclusions: These results suggested that chronic ethanol ingestion resulted in a progressive depletion of mitochondrial GSH and sensitization of type II cells to inflammatory mediator-induced apoptosis and necrosis. These effects may be particularly relevant during acute stress when proliferation and differentiation of these cells are critical to repair of the damaged alveolar epithelium and may have important ramifications for the treatment of acute respiratory distress syndrome in patients with a history of alcohol. abuse.