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Am. J. Respir. Cell Mol. Biol., Volume 18, Number 1, January, 1998 91-99

Fluticasone Propionate Attenuates Ozone-induced Rhinitis and Mucous Cell Metaplasia in Rat Nasal Airway Epithelium

Jon A. Hotchkiss, Roger Hilaski, Hyeyoun Cho, Karen Regan, Patty Spencer, Kate Slack, and Jack R. Harkema

Department of Pathology, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan; MPI Research, Mattawan, Michigan; and Glaxo Wellcome, Inc., Research Triangle Park, North Carolina

Ozone (O3) is the principal oxidant pollutant in photochemical smog. Repeated exposures to O3 induces inflammation and mucous cell metaplasia in the nasal airways of laboratory animals. Our study was designed to determine the efficacy of a topical anti-inflammatory corticosteroid in preventing O3-induced rhinitis and mucous cell metaplasia in rat nasal epithelium. Male F344 rats were exposed to filtered air (0 ppm O3; air-controls) or 0.5 ppm O3, 8 h/day, for 3 or 5 days. Immediately before and after each exposure, rats received an intranasal instillation (50 µl/nasal passage) of a topical corticosteroid, fluticasone propionate (FP; 25 µg/nasal passage) or its vehicle only (0.01% ethanol in saline). Rats were killed 2 h after the third exposure (3-day exposure) or 3 days after the fifth exposure (5-day exposure) and nasal tissues were processed for light microscopy. Numeric densities of epithelial cells and neutrophils, and the amount of intraepithelial mucosubstances (IM) in the epithelium lining the maxilloturbinates were morphometrically determined. There were no significant differences in any measured parameter in air-exposed rats instilled with FP compared with air-exposed rats instilled with vehicle. Vehicle-treated rats exposed to ozone had neutrophilic rhinitis with 3.3- and 1.6-fold more intraepithelial neutrophils (3-day and 5-day exposure, respectively) and marked mucous cell metaplasia (5-day exposure only) with numerous mucous cells and approximately 60 times more IM in the nasal transitional epithelium compared with vehicle-treated air-controls. FP-treated rats exposed to ozone had minimal nasal inflammation (1.3-fold more intraepithelial neutrophils only after 3-day exposure) and minimal mucous cell metaplasia (5-fold more IM only after 5-day exposure) compared with vehicle-instilled, air-exposed rats. Results of this study indicate that FP-treatment is effective in attenuating not only O3-induced rhinitis (30-60% reduction) but also O3-induced mucous cell metaplasia (85% reduction) in rat nasal transitional epithelium. The cellular and molecular mechanisms involved in FP-induced attenuation of O3-induced nasal lesions remain to be determined.




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Copyright © 1998 American Thoracic Society.