EXPRESSION OF THE BCL-2 PROTEIN IN NASAL EPITHELIA OF F344 N RATS DURING MUCOUS CELL METAPLASIA AND REMODELING/

Exposure to ozone induces mucous cell metaplasia in rat airway epithel ia, During the regeneration process, apoptotic mechanisms may be respo nsible for eliminating metaplastic cells. Therefore, the present study investigated expression of Bcl-2, a regulator of apoptosis. in ozone- induced mucous cell metaplasias. Adjacent metaplastic mucous cells in nasal airway epithelia that were exposed to ozone were heterogeneous i n their expression of Bcl-2; some cells expressed high levels, whereas others expressed low levels or no Bcl-2, On Western blot analysis, Bc l-2 was detected in protein extracts from nasal epithelia of mts expos ed to 0.5 ppm ozone for 1 mo but not in control rats exposed to filter ed air. The number of metaplastic mucous cells in transitional epithel ia of rat nasal airways was increased from 0 to about 200 after 3 and 6 mo of exposure to ozone, only 0 to 10 metaplastic mucous cells remai ned after a recovery period of 13 wk in rats exposed to ozone for 3 mo . The number of mucous cells of the respiratory epithelium lining the midseptum did not change after ozone exposure or recovery. The percent age of Bcl-2-positive cells lining the midseptum increased from 7 to 1 4% after a 3- and 6-mo ozone exposure, respectively. In transitional e pithelia of the lateral wall and the nasotorbinates and maxilloturbina tes, 35 to 55% of cells were Bcl-2-positive after a 1-mo exposure and 10 to 18% after both a 3- and a 6-mo exposure to ozone. Bcl-2 reactivi ty decreased to 0 to 8% after a recovery period of 13 wk. These observ ations suggest that Bcl-2 plays a role in the development and resoluti on of mucous cell metaplasias. This model may be useful in uncovering the role of Bcl-2 during the development and maintenance of metaplasti c mucous cells. Disregulation of Bcl-2 expression may be responsible f or the sustained mucous cell metaplasia in asthmatics or may allow cel ls to accumulate and become more susceptible to transformation leading to neoplasia.