Article Text

  1. A. L. Fernandez,
  2. P. C. Joshi,
  3. D. M. Guidot
  1. Atlanta, GA.


Chronic alcohol abuse impairs alveolar macrophage immune function and renders patients susceptible to severe pneumonia and acute lung injury. Macrophage maturation and immune function require priming by granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced by the alveolar epithelium and signals to the macrophage via specific cell surface receptors. The GM-CSF receptor is composed of a binding subunit (GM-CSFRα) and a signaling subunit (GM-CSFRβ), which must be coordinately expressed and inserted into the cell surface membrane in order for the macrophage to respond to GM-CSF stimulation. However, the effects of alcohol abuse on GM-CSF-dependent priming of the alveolar macrophage have not been examined. Therefore, we hypothesized that chronic ethanol ingestion interferes with GM-CSF signaling to the alveolar macrophage. To test this hypothesis, we first compared GM-CSF expression in the alveolar epithelium of rats fed an isocaloric liquid diet containing either ethanol or maltin-dextrin (control diet) for 6 weeks. We then examined alveolar macrophage cellular expression as well as membrane localization of each GM-CSF receptor subunit. Chronic ethanol ingestion had no effect on GM-CSF gene expression in alveolar epithelial cells (by PCR) or protein levels in the alveolar lining fluid (by ELISA). In parallel, chronic ethanol ingestion had no effect on GM-CSFRα or GM-CSFRβ gene or protein expression (by PCR and Western blot analysis, respectively) within the alveolar macrophages. However, chronic ethanol ingestion significantly decreased macrophage cell surface expression of both the GM-CSFRα and GM-CSFRβ subunits by ˜ 50% (by flow cytometry). In contrast, macrophage cell surface expression of the interleukin-6 receptor was the same in control-fed and ethanol-fed rats, suggesting that the defect in GM-CSF receptor expression is relatively specific. We conclude that chronic ethanol ingestion decreases macrophage cell surface expression of the GM-CSF receptor. Although ethanol ingestion has no effect on the expression of GM-CSF within the alveolar epithelium and does not inhibit cellular expression of the GM-CSF receptors in alveolar macrophages per se, it appears to interfere with trafficking and/or insertion of the GM-CSF receptor into the cell surface membrane. We speculate that GM-CSF treatment could improve alveolar macrophage immune function in critically ill patients with alcohol abuse and thereby decrease the morbidity and/or mortality associated with severe pneumonia or acute lung injury in these highly vulnerable patients.

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.