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Published ahead of print on April 22, 2004, doi:10.1164/rccm.200304-478OC
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American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 188-194, (2004)
© 2004 American Thoracic Society

Original Article

Transforming Growth Factor ß1 Expression and Activation Is Increased in the Alcoholic Rat Lung

Rabih I. Bechara, Lou Ann S. Brown, Jesse Roman, Pratibha C. Joshi and David M. Guidot

Section of Pulmonary and Critical Care Medicine, Atlanta VA Medical Center, Decatur; and Division of Pulmonary, Allergy and Critical Care Medicine and Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia

Correspondence and reprint requests should be addressed to David M. Guidot, M.D., Atlanta VAMC, (151-P), 1670 Clairmont Road, Decatur, GA 30033. E-mail: dguidot{at}emory.edu

Alcohol abuse increases the incidence of acute respiratory distress syndrome more than threefold in patients with septic shock. We have shown that chronic ethanol ingestion in a rat model impairs alveolar epithelial barrier function and enhances lung injury during sepsis. We speculated that transforming growth factor ß1 (TGFß1), a pluripotent cytokine implicated in models of epithelial barrier disruption and lung injury, could mediate alveolar epithelial injury in the alcoholic lung. We report that chronic ethanol ingestion (6 weeks) in rats increased both TGFß1 mRNA and protein tissue expression (p < 0.05), but alone did not induce the release of TGFß1 into the alveolar space. However, during endotoxemia, ethanol-fed rats released fivefold more TGFß1 protein (by ELISA, p < 0.05) into the alveolar space than control-fed rats. Furthermore, lung lavage fluid from endotoxemic, ethanol-fed rats had more biologically active TGFß1 protein than control-fed rats (p < 0.05), as reflected by anti-TGFß1 antibody-inhibitable induction of permeability in rat alveolar epithelial monolayers in vitro. We conclude that chronic ethanol ingestion increases lung expression of TGFß1, which, during endotoxemia, is released and activated in the alveolar space in which it can disrupt the normally tight epithelial barrier. We speculate that this mechanism could contribute to the increased risk of acute respiratory distress syndrome in alcoholic patients.

Key Words: acute respiratory distress syndrome • alcoholism • alveolar type II cell • epithelium • sepsis




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