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n the claudin proteins are disrupted, the lung leaks more, the researchers have found. The lung can usually pump out this excess fluid, but when the lung suffers an injury or infection it is unable to handle the greater volume, Koval explained. And that's when pneumonia or ARDS may develop.

The researchers also previously found that the alcoholic lung has fewer granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors and a dampened response to signaling by GM-CSF in the epithelial cells, which form the lining inside the lung. GM-CSF is a hormone that plays a role in immunity within the lung.

The researchers keyed into GM-CSF after a clinical study found that GM-CSF treatment appeared to decrease acute lung injury in patients with septic shock. They have found that lung epithelial cells depend on GM-CSF signaling to maintain the tight barrier that is critical for gas exchange. They have also found that the air-fluid barrier is enhanced when the alcoholic lung is treated with GM-CSF.

GM-CSF connection strengthened

With these findings in mind, the researchers fed rats an alcohol-containing liquid diet for six weeks to mimic chronic alcohol abuse. They then applied GM-CSF to epithelial cells impaired by the rats' alcohol ingestion. They found that GM-CSF restores claudin protein function and the cells' air-fluid barrier function improved. These findings complement their recently published study showing that this same GM-CSF treatment restores immune function in alcohol-fed rats.

"These findings suggest that alcohol abuse dampens GM-CSF signaling, which, in turn, contributes to the alcoholic lung phenotype and renders the lung susceptible to edematous injury," the authors wrote. Treating lung epithelial cells with GM-CSF can reverse the deleterious effects of alcohol, the authors concluded. "GM-CSF treatment, in part by restoring tight junction protein assembly, may decrease the risk of acute lung injury in
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Contact: Christine Guilfoy
cguilfoy@the-aps.org
301-634-7253
American Physiological Society
3-Nov-2006

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