Zinc deficiency mediates alcohol-induced alveolar epithelial and macrophage dysfunction in rats.
Chronic alcohol abuse impairs both alveolar epithelial and macrophage function, and renders individuals susceptible to acute lung injury, pneumonia, and other serious lung diseases. Zinc deficiency, which is known to impact both epithelial and immune cell functions, is also associated with alcohol abuse. In this study, chronic alcohol ingestion (6 wk) in rats altered expression of key zinc transporters and storage proteins in the small intestine and the lung, and decreased zinc levels in the alveolar compartment. Zinc supplementation of alveolar epithelial monolayers derived from alcohol-fed rats in vitro, or of the diets of alcohol-fed rats in vivo, restored alveolar epithelial barrier function, and these improvements were associated with salutary changes in tight junction protein expression and membrane localization. In parallel, dietary zinc supplementation increased intracellular zinc levels, GM-CSF receptor expression, and bacterial phagocytic capacity in the alveolar macrophages of alcohol-fed rats. Together, these studies implicate zinc deficiency as a novel mechanism mediating alcohol-induced alveolar epithelial and macrophage dysfunction. Importantly, these findings argue that dietary supplementation can overcome alcohol-induced zinc deficiency and restore alveolar epithelial and macrophage function, and therefore could be an effective treatment for the susceptible alcoholic lung phenotype.
Joshi
Pratibha C
PC
Atlanta Veterans Affairs Medical Center-VAMC (151-P), 1670 Clairmont Road, Decatur, GA 30033, USA. pcjoshi@emory.edu
Mehta
Ashish
A
Jabber
Wissam S
WS
Fan
Xian
X
Guidot
David M
DM
D000437:Alcoholism / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins; D002460:Cell Line; D019587:Dietary Supplements; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015032:Zinc / Q000172:deficiency*; D062826:Zonula Occludens-1 Protein
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C568985:OCLN protein, human; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; C491596:Slc30a4 protein, rat; C569042:TJP1 protein, human; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C092392:Slc30a1 protein, rat; D000431:Ethanol; D008668:Metallothionein; D015032:Zinc