Alcohol induced mitochondrial oxidative stress and alveolar macrophage dysfunction.
Alcohol induced mitochondrial oxidative stress and alveolar macrophage dysfunction.
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DOI：
10.1155/2014/371593
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发表时间：
2014
影响因子：
--
通讯作者：
Brown LA
中科院分区：
文献类型：
--
作者：
Liang Y;Harris FL;Brown LA
酒精使用障碍会增加侵袭性和耐药性社区获得性肺炎和结核病的风险。由于肺泡巨噬细胞（AM）协调肺泡腔中的免疫反应，因此了解酒精抑制AM吞噬作用的潜在机制对改善临床结果至关重要。在肺泡腔中，慢性酒精摄入会导致严重的氧化应激，并消耗对AM功能至关重要的抗氧化剂。它在维持细胞氧化还原平衡和提供吞噬作用所必需的ATP方面起重要作用。本研究的重点是了解酒精如何触发线粒体活性氧（ROS），刺激细胞氧化应激，并诱导AM功能障碍。本研究还研究了线粒体靶向抗氧化剂mitoTEMPOL（mitoT）在调节线粒体氧化应激和AM功能障碍中的能力。使用体外乙醇暴露和来自乙醇喂养小鼠的AM，乙醇促进线粒体功能障碍，包括线粒体ROS增加，线粒体膜电位降低和ATP降低。用mitoT治疗逆转了这些效应。乙醇诱导的吞噬作用和细胞活力下降也与mitoT减弱。因此，针对线粒体的抗氧化剂具有改善乙醇诱导的线粒体氧化应激和随后的AM吞噬作用和细胞活力降低的潜力。
An alcohol use disorder increases the risk of invasive and antimicrobial resistant community-acquired pneumonia and tuberculosis. Since the alveolar macrophage (AM) orchestrates the immune response in the alveolar space, understanding the underlying mechanisms by which alcohol suppresses AM phagocytosis is critical to improving clinical outcomes. In the alveolar space, chronic alcohol ingestion causes severe oxidative stress and depletes antioxidants which are critical for AM function. The mitochondrion is important in maintaining cellular redox balance and providing the ATP critical for phagocytosis. The focus of this study was to understand how alcohol triggers mitochondrial reactive oxygen species (ROS), stimulates cellular oxidative stress, and induces AM dysfunction. The current study also investigated the capacity of the mitochondrial targeted antioxidant, mitoTEMPOL (mitoT), in modulating mitochondrial oxidative stress, and AM dysfunction. Using in vitro ethanol exposure and AMs from ethanol-fed mice, ethanol promoted mitochondrial dysfunction including increased mitochondrial ROS, decreased mitochondrial membrane potential, and decreased ATP. Treatment with mitoT reversed these effects. Ethanol-induced decreases in phagocytosis and cell viability were also attenuated with mitoT. Therefore, antioxidants targeted to the mitochondria have the potential to ameliorate ethanol-induced mitochondrial oxidative stress and subsequent decreases in AM phagocytosis and cell viability.
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DOI：
10.1073/pnas.0510977103
发表时间：
2006-05-16
影响因子：
11.1
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影响因子：
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影响因子：
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