Effects of pre-existing rhinitis on ozone-induced mucous cell metaplasia in rat nasal epithelium

Ozone causes rhinitis and nasal epithelial alterations. The toxicity of ozo ne on nasal airways with pre-existing rhinitis has not been investigated. T he present study was designed to determine the effect of endotoxin-induced rhinitis on ozone-induced epithelial alterations, especially mucous cell me taplasia (MCM), in the nasal transitional epithelium (NTE) of rats. Six h p rior to daily inhalation exposure, male F344/N rats were intranasally insti lled with saline or endotoxin (100 mu g/day). Rats were killed 2 h or 4 day s after 3-day (8 h/day) exposure to ozone (0.5 ppm) or filtered air (0 ppm) . The maxilloturbinate from one nasal passage was processed for morphometri c analyses of the numbers of neutrophils and epithelial cells and the amoun t of intraepithelial mucosubstances (IM) in the NTE. The maxilloturbinate f rom the other nasal passage was processed for a mucin-specific (rMuc-5AC) m RNA analysis. At 2 h postexposure, endotoxin/ozone-exposed rats had 48 and 3 times more neutrophils in the NTE than did saline/air- and saline/ozone-e xposed rats, respectively, Ozone-exposed rats had 35% more NTE cells and 2- fold more mucin mRNA than did saline/air-exposed rats, independent of endot oxin exposure. At 4 days postexposure, endotoxin/ozone-exposed rats had 5 a nd 2 times more IM and mucous cells, respectively, than did saline/air- and saline/ozone-exposed rats. Though endotoxin/air-exposed rats killed at 2 h postexposure had more neutrophils (40-fold), epithelial cells (27%) and mu cin mRNA (2-fold) in the NTE than did saline/air-exposed rats, no MCM was p resent in those rats killed at 4 days postexposure. The results of the pres ent study indicated that pre-existing rhinitis augments ozone-induced MCM. (C) 1999 Academic Press.