title: Expression of the Bcl-2 protein in nasal epithelia of F344/N rats during mucous cell metaplasia and remodeling.
abstract: Exposure to ozone induces mucous cell metaplasia in rat airway epithelia. During the regeneration process, apoptotic mechanisms may be responsible 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 in their expression of Bcl-2; some cells expressed high levels, whereas others expressed low levels or no Bcl-2. On Western blot analysis, Bcl-2 was detected in protein extracts from nasal epithelia of rats exposed to 0.5 ppm ozone for 1 mo but not in control rats exposed to filtered air. The number of metaplastic mucous cells in transitional epithelia 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 remained 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 percentage of Bcl-2-positive cells lining the midseptum increased from 7 to 14% after a 3- and 6-mo ozone exposure, respectively. In transitional epithelia of the lateral wall and the nasoturbinates and maxilloturbinates, 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 reactivity decreased to 0 to 8% after a recovery period of 13 wk. These observations suggest that Bcl-2 plays a role in the development and resolution of mucous cell metaplasias. This model may be useful in uncovering the role of Bcl-2 during the development and maintenance of metaplastic mucous cells. Disregulation of Bcl-2 expression may be responsible for the sustained mucous cell metaplasia in asthmatics or may allow cells to accumulate and become more susceptible to transformation leading to neoplasia.
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87185, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tesfaigzi
authors.forename: J A
authors.initials: JA
authors.lastname: Hotchkiss
authors.forename: J R
authors.initials: JR
authors.lastname: Harkema
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008679:Metaplasia / Q000139:chemically induced / Q000378:metabolism; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010126:Ozone / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D010126:Ozone