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 β 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.
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 β 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.
Authors: Marc Moss; Polly E Parsons; Kenneth P Steinberg; Leonard D Hudson; David M Guidot; Ellen L Burnham; Stephanie Eaton; George A Cotsonis Journal: Crit Care Med Date: 2003-03 Impact factor: 7.598
Authors: D M Guidot; K Modelska; M Lois; L Jain; I M Moss; J F Pittet; L A Brown Journal: Am J Physiol Lung Cell Mol Physiol Date: 2000-07 Impact factor: 5.464
Authors: M Moss; D M Guidot; M Wong-Lambertina; T Ten Hoor; R L Perez; L A Brown Journal: Am J Respir Crit Care Med Date: 2000-02 Impact factor: 21.405
Authors: Michael F Mayo-Smith; Lee H Beecher; Timothy L Fischer; David A Gorelick; Jeanette L Guillaume; Arnold Hill; Gail Jara; Chris Kasser; John Melbourne Journal: Arch Intern Med Date: 2004-07-12
Authors: Abdel A Alli; Elizabeth M Brewer; Darrice S Montgomery; Marcus S Ghant; Douglas C Eaton; Lou Ann Brown; My N Helms Journal: Am J Physiol Lung Cell Mol Physiol Date: 2014-03-28 Impact factor: 5.464
Authors: Anatoly V Skalny; Margarita G Skalnaya; Andrei R Grabeklis; Anastasia A Skalnaya; Alexey A Tinkov Journal: Eur J Nutr Date: 2017-11-24 Impact factor: 5.614
Authors: Abigail R Cannon; Niya L Morris; Adam M Hammer; Brenda Curtis; Daniel G Remick; Samantha M Yeligar; Lauren Poole; Ellen L Burnham; Todd A Wyatt; Patricia E Molina; Kaku So-Armah; Trinidad Cisneros; Guoshun Wang; Charles H Lang; Pranoti Mandrekar; Elizabeth J Kovacs; Mashkoor A Choudhry Journal: Alcohol Date: 2016-07-25 Impact factor: 2.405