Toxicological Sciences 67, 284-294 (2002)
Copyright © 2002 by the Society of Toxicology
RESPIRATORY TOXICOLOGY |
Enhancement of Nasal Inflammatory and Epithelial Responses after Ozone and Allergen Coexposure in Brown Norway Rats
Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan 48824
Repeated exposures to ozone cause inflammation and mucous cell metaplasia (MCM) in the nasal mucosa of laboratory animals. Similar cellular responses occur in humans during allergic rhinitis. We tested the hypothesis that exposure to ozone will enhance the inflammatory and epithelial responses associated with allergic rhinitis. Ovalbumin (OVA)-sensitized Brown Norway rats were exposed to ozone (0.5 ppm, 8 h/day) for 1 day or 3 consecutive days. Immediately after each ozone exposure, animals were challenged intranasally (IN) with either sterile saline or OVA dissolved in saline (1%, 50 µl/nasal passage). Twenty-four h after the last IN challenge rats were sacrificed; nasal tissues were removed and processed for light microscopic examination and morphometric analysis of numeric densities of inflammatory and epithelial cell populations and volume densities of intraepithelial mucosubstances. A single OVA challenge caused a significant influx of neutrophils and eosinophils into the submucosa of all nasal tissues. Ozone exposure further enhanced the appearance of eosinophils in the maxilloturbinates of OVA-challenged rats but did not increase inflammation in other nasal tissues. After 3 days of ozone/OVA coexposures, the nasal transitional epithelium lining the maxilloturbinates had increased numbers of epithelial cells as well as the appearance of mucus-containing cells in areas normally absent of these secretory cells (i.e., MCM). Multiple challenges with OVA caused increased epithelial mucosubstances in the respiratory epithelium lining the septum without increasing the number of epithelial cells. Multiple exposures to both ozone and OVA caused greater increases in intraepithelial mucosubstances in the septum than those elicited by OVA alone. These results demonstrate that exposure to ozone exacerbates epithelial and inflammatory responses associated with allergen challenge. In addition, coexposure of these agents enhanced the induced production of nasal mucosubstances caused by either agent alone.
Key Words: ozone; allergen; ovalbumin; mucous cell metaplasia; eosinophil; neutrophil; inflammation.
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