Alcoholism Causes Alveolar Macrophage Zinc Deficiency and Immune Dysfunction
Alcoholism Causes Alveolar Macrophage Zinc Deficiency and Immune Dysfunction
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DOI：
10.1164/rccm.201301-0061oc
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发表时间：
2013-09-15
影响因子：
24.7
通讯作者：
Guidot, David M.
中科院分区：
文献类型：
--
作者：
Mehta, Ashish J.;Yeligar, Samantha M.;Guidot, David M.
基本原理：酒精使用障碍导致下呼吸道氧化应激，增加对肺炎和肺损伤的易感性。目前，没有治疗方案存在，以减轻肺的后果alcoholis.Objectives：我们最近确定的动物模型，酒精摄入损害肺锌代谢，并导致肺泡巨噬细胞免疫功能障碍。本研究的目的是确定酒精中毒对人类受试者锌生物利用度和肺泡巨噬细胞功能的影响。我们招募了其他方面健康的酗酒者（n = 17）和匹配的对照受试者（n = 17），他们接受了支气管镜检查以分离肺泡巨噬细胞，分析了细胞内锌，吞噬功能，和粒细胞-巨噬细胞集落刺激因子受体的表面表达;所有这三个指标在实验模型中均降低。酗酒者血清锌正常，但肺泡巨噬细胞内锌水平显着降低（校正平均值[SE]，718 [41] vs. 948 [25] RFU/细胞; P < 0.0001）;细菌吞噬作用（校正平均值[SE]，1，027 [48] vs. 1，509 [76] RFU/cell; P < 0.0001）;和粒细胞-巨噬细胞集落刺激因子受体β亚基的表达（调整平均值[SE]，1，471 [42] vs. 2，114 [35] RFU/细胞; P < 0.0001]。在体外用醋酸锌和谷胱甘肽处理肺泡巨噬细胞可增加细胞内锌水平并改善其吞噬功能。这些新的临床发现提供了证据表明，酒精滥用与肺泡腔内严重的锌缺乏和免疫功能障碍有关，并表明饮食中补充锌和谷胱甘肽前体可以增强气道先天免疫，降低肺炎或肺结核的风险。伤害这些脆弱的人。
Rationale: Alcohol use disorders cause oxidative stress in the lower airways and increase susceptibility to pneumonia and lung injury. Currently, no therapeutic options exist to mitigate the pulmonary consequences of alcoholism.Objectives: We recently determined in an animal model that alcohol ingestion impairs pulmonary zinc metabolism and causes alveolar macrophage immune dysfunction. The objective of this research is to determine the effects of alcoholism on zinc bioavailability and alveolar macrophage function in human subjects.Methods: We recruited otherwise healthy alcoholics (n = 17) and matched control subjects (n = 17) who underwent bronchoscopy for isolation of alveolar macrophages, which were analyzed for intracellular zinc, phagocytic function, and surface expression of granulocyte-macrophage colony-stimulating factor receptor; all three of these indices are decreased in experimental models.Measurements and Main Results: Alcoholic subjects had normal serum zinc, but significantly decreased alveolar macrophage intracellular zinc levels (adjusted means [SE], 718 [41] vs. 948 [25] RFU/cell; P < 0.0001); bacterial phagocytosis (adjusted means [SE], 1,027 [48] vs. 1,509 [76] RFU/cell; P < 0.0001); and expression of granulocyte-macrophage colony-stimulating factor receptor beta subunit (adjusted means [SE], 1,471 [42] vs. 2,114 [35] RFU/cell; P < 0.0001]. Treating alveolar macrophages with zinc acetate and glutathione in vitro increased intracellular zinc levels and improved their phagocytic function.Conclusions: These novel clinical findings provide evidence that alcohol abuse is associated with significant zinc deficiency and immune dysfunction within the alveolar space and suggest that dietary supplementation with zinc and glutathione precursors could enhance airway innate immunity and decrease the risk for pneumonia or lung injury in these vulnerable individuals.