Molecular biological mechanism of alcohol-induced asthma

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Approximately half of Japanese asthmatics experience exacerbation of asthma after alcohol consumption. We previously reported that this phenomenon is probably caused by histamine release from mast cells by acetaldehyde stimulation. However, no reports have described the effects of acetaldehyde on human airway mast cells. The purpose of the first study was to demonstrate acetaldehyde-induced histamine release from human airway mast cells with subsequent airway smooth muscle contraction and investigate the mechanism of such action. Human lung tissue samples were prepared from resected lungs of patients with lung cancer. The effect of acetaldehyde on airway muscle tone and the concentration of chemical mediators released in the organ bath were measured before and after acetaldehyde stimulation. Mast cells were prepared from lung parenchyma by the immunomagnetic method and then stimulated with acetaldehyde to determine the released chemical mediators. Acetaldehyde (>3x10^<>-4M) increased a … More irway muscle tone, which was associated with a significant increase in the release of histamine, but not thromboxane B2 or cysteinyl-leukotrienes. A histamine antagonist completely inhibited acetaldehyde-induced bronchial smooth muscle contraction. Acetaldehyde also induced a significant histamine release from human lung mast cells, and degranulation of mast cells. The present results strongly suggest that acetaldehyde stimulates human airway mast cells to release histamine, and this histamine may be involved in bronchial smooth muscle contraction following alcohol consumption. Acetaldehyde is also found in cigarette smoke and may cause airway inflammation. The purpose of the second study was to determine the effect of acetaldehyde on cytokine production and NF-κB activation in human bronchial tissues. Human bronchi were prepared from normal parts of lung tissues resected for lung cancer. The bronchi were cultured in the presence of 5x10^<-4>M of acetaldehyde for 24 hours and the concentrations of eotaxm, GM-CSF, IL-5, IL-8 and RANTES in cultured supernatants were determined by ELISA. Tissues were also immunohistochemically stained for NF-κBp65. Acetaldehyde significantly increased GM-CSF production from human bronchi and nuclear translocation of NF-κBp65 in airway epithelium, but had no effects on other cytokines. Our findings suggest that acetaldehyde potentially causes airway inflammation via increased GM-CSF production through nuclear translocation of NF-κB. Less