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The Proceedings of the American Thoracic Society 5:368-369 (2008)
© 2008 The American Thoracic Society
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Effects of Alcohol and GM-CSF on Alveolar Tight Junctions

Michael Koval1, Xian Fan2, Alberto L. Fernandez1,2, Latoya N. Johnson1, Pratibha C. Joshi1,2 and David M. Guidot1,2

1 Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia; and 2 VA Medical Center, Decatur, Georgia

Correspondence and requests for reprints should be addressed to Michael Koval, Ph.D., Emory University School of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Whitehead Biomedical Research Building, Suite 205, 615 Michael St., Atlanta, GA 30322. E-mail: mhkoval{at}emory.edu

Alcohol abuse predisposes individuals to acute lung injury (ALI), and the alcoholic lung phenotype is characterized by abnormal alveolar epithelial tight junction permeability. Using a rat model, we have found that chronic alcohol ingestion causes hallmark changes in tight junction protein expression, with claudin-1 and claudin-7 decreased and claudin-5 increased. Importantly, claudin localization to alveolar epithelial tight junctions also was impaired by alcohol ingestion. Previously, we found that the granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling pathway is dampened in the alcoholic lung and that GM-CSF rapidly reverses the leaky alveolar epithelial phenotype (1). Here, we found that alveolar epithelial cells isolated from alcohol-fed rats directly respond to GM-CSF by increasing localization of claudins, occludin, and zona occludens-1 to tight junctions and increasing occludin expression threefold. This suggests that restoration of tight junction protein assembly by alveolar epithelial cells may contribute to the beneficial effect of GM-CSF on lung function and thus potentially decrease the risk of ALI for susceptible individuals.

FOOTNOTES

Supported by a Merit Review from the Department of Veterans Affairs, the National Institute on Alcohol Abuse and Alcoholism (P50 AA013757 [GenBank] , T32 AA013528), the National Heart Lung and Blood Institute (R01 HL083120) (to M.K.), and the Emory University Research Committee.

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form August 23, 2007; accepted in final form October 16, 2007)

REFERENCES

  1. Joshi PC, Applewhite L, Mitchell PO, Fernainy K, Roman J, Eaton DC, Guidot DM. GM-CSF receptor expression and signaling is decreased in lungs of ethanol-fed rats. Am J Physiol Lung Cell Mol Physiol 2006;291:L1150–L1158.[Abstract/Free Full Text]




This Article
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