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 ozone on nasal airways with pre-existing rhinitis has not been investigated. The present study was designed to determine the effect of endotoxin-induced rhinitis on ozone-induced epithelial alterations, especially mucous cell metaplasia (MCM), in the nasal transitional epithelium (NTE) of rats. Six h prior to daily inhalation exposure, male F344/N rats were intranasally instilled with saline or endotoxin (100 microgram/day). Rats were killed 2 h or 4 days 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 morphometric analyses of the numbers of neutrophils and epithelial cells and the amount of intraepithelial mucosubstances (IM) in the NTE. The maxilloturbinate from the other nasal passage was processed for a mucin-specific (rMuc-5AC) mRNA 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-exposed rats, respectively. Ozone-exposed rats had 35% more NTE cells and 2-fold more mucin mRNA than did saline/air-exposed rats, independent of endotoxin exposure. At 4 days postexposure, endotoxin/ozone-exposed rats had 5 and 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 mucin mRNA (2-fold) in the NTE than did saline/air-exposed rats, no MCM was present in those rats killed at 4 days postexposure. The results of the present study indicated that pre-existing rhinitis augments ozone-induced MCM.