Alcohol and lung injury and immunity.
Alcohol and lung injury and immunity.
复制标题
DOI：
10.1016/j.alcohol.2016.08.005
复制
发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Brown LA
中科院分区：
文献类型：
--
作者：
Yeligar SM;Chen MM;Kovacs EJ;Sisson JH;Burnham EL;Brown LA
每年，过度饮酒造成超过2200亿美元的经济损失和8万人死亡，使过度饮酒成为美国第三大生活方式相关死亡原因。患有酒精使用障碍（AUD）的患者对呼吸道病原体和肺损伤的易感性也增加，包括急性呼吸窘迫综合征（ARDS）的风险增加2-4倍。本文综述了酒精引起肺损伤和损害肺免疫的一些潜在机制。在烧伤中毒个体中，肠-肝轴的激活驱动肺部炎症，从而对发病率和死亡率产生负面影响。在肺中，上气道是酒精诱导的肺免疫功能障碍期间微生物清除失败的第一个检查点。短暂和长时间的酒精暴露驱动控制纤毛功能的新蛋白质的不同翻译后修饰。蛋白质组学方法需要确定新的酒精目标和翻译后修饰的气道纤毛参与酒精依赖性信号转导途径。当上呼吸道不能清除吸入的病原体时，它们进入肺泡腔，在那里它们主要被肺泡巨噬细胞（AM）清除。随着慢性酒精摄入，AM中的氧化应激途径被刺激，从而损害AM免疫能力和病原体清除。肺炎球菌性肺炎和AUDs的流行病学已得到很好的确立，因为已报告了易感性和疾病严重程度的增加。AUD受试者对肺炎球菌肺炎感染的易感性增加，这可能是由于AM的促炎反应，导致氧化应激增加。
Annually, excessive alcohol use accounts for more than $220 billion in economic costs and 80,000 deaths, making excessive alcohol use the third leading lifestyle-related cause of death in the US. Patients with an alcohol-use disorder (AUD) also have an increased susceptibility to respiratory pathogens and lung injury, including a 2–4-fold increased risk of acute respiratory distress syndrome (ARDS). This review investigates some of the potential mechanisms by which alcohol causes lung injury and impairs lung immunity. In intoxicated individuals with burn injuries, activation of the gut-liver axis drives pulmonary inflammation, thereby negatively impacting morbidity and mortality. In the lung, the upper airway is the first checkpoint to fail in microbe clearance during alcohol-induced lung immune dysfunction. Brief and prolonged alcohol exposure drive different post-translational modifications of novel proteins that control cilia function. Proteomic approaches are needed to identify novel alcohol targets and post-translational modifications in airway cilia that are involved in alcohol-dependent signal transduction pathways. When the upper airway fails to clear inhaled pathogens, they enter the alveolar space where they are primarily cleared by alveolar macrophages (AM). With chronic alcohol ingestion, oxidative stress pathways in the AMs are stimulated, thereby impairing AM immune capacity and pathogen clearance. The epidemiology of pneumococcal pneumonia and AUDs is well established, as both increased predisposition and illness severity have been reported. AUD subjects have increased susceptibility to pneumococcal pneumonia infections, which may be due to the pro-inflammatory response of AMs, leading to increased oxidative stress.