The role of apoptotic regulators in metaplastic mucous cells

Exposure of airways to environmental toxins or allergens induces proliferation of epithelial cells. Depending on the type of exposure, existing and newly formed cells can differentiate into mucus-producing cells resulting in mucous cell metaplasia (MCM). During recovery, the epithelium reduces the number of epithelial cells to return to the original state. Understanding the mechanisms involved in this resolution could be useful in deleting mucous cells and, thereby, mucous secretions. We have found that metaplastic mucous cells induced by exposure to ozone, endotoxin, cigarette smoke or allergens in epithelia of various regions of the airways express Bcl-2, a regulator of apoptosis, and neutrophils appear to be involved in its expression. The percentage of Bcl-2-positive mucous cells is decreased prior to the resolution of MCM. Furthermore, targeted reduction of Bcl-2 expression causes a dose-dependent reduction of epithelial mucous cells, suggesting that Bcl-2 is involved in maintaining metaplastic mucous cells. Horses with recurrent airway obstruction show an increased percentage of Bcl-2-positive mucous cells compared to their normal counterparts. These studies suggest that down-regulation of Bcl-2 expression may be useful to reduce mucous secretions in diseased subjects. The role of Bax in the reduction of MCM during prolonged exposure to allergen is also discussed.