Repeated episodes of ozone inhalation attenuates airway injury/repair and release of substance P, but not adaptation

• Published in: Toxicology and applied pharmacology 2003-02, Vol.186 (3), p.127-142
• Main Authors: Schelegle, Edward S, Walby, William F, Alfaro, Mario F, Wong, Viviana J, Putney, Lei, Stovall, Mary Y, Sterner-Kock, Anja, Hyde, Dallas M, Plopper, Charles G
• Format: Article
• Language: English
• Subjects: Adaptation; Adaptation, Physiological - drug effects; Administration, Inhalation; Air; Airway injury; Animals; Biological and medical sciences; Bronchi - drug effects; Bronchi - metabolism; Bronchi - pathology; Bronchoalveolar Lavage; Cell Division - drug effects; Environmental pollutants toxicology; Episodic exposure; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Epithelium - drug effects; Epithelium - metabolism; Epithelium - pathology; Logistic Models; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; Medical sciences; Oxidants, Photochemical - administration & dosage; Oxidants, Photochemical - toxicity; Ozone; Ozone - administration & dosage; Ozone - toxicity; Rats; Repair; Respiration - drug effects; Substance P; Substance P - metabolism; Time Factors; Toxicology; Trachea - drug effects; Trachea - metabolism
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/S0041-008X(02)00026-1

To determine the impact of repeated episodes of ozone exposure on physiologic adaptation, epithelial injury/repair, and tracheal substance P levels, adult rats were subjected to episodes of ozone (5 days, 1 ppm, 8 h/day) followed by 9 days of filtered air for four cycles. Rats were sampled on days 1 and 5 of each episode and 9 days after day 5 of episodes 1, 2, and 4. One hour before being euthanized each rat was injected with 5-bromo-2′-deoxyuridine to label proliferating cells. Each 5-day episode showed a characteristic pattern of rapid shallow breathing (days 1 and 2), epithelial injury, and interstitial and intraluminal inflammation. In contrast, the neutrophil component of inflammation, tracheal substance P release, and cell proliferation became attenuated with each consecutive episode of exposure. Concurrent with this cyclic and attenuated response there was progressive hypercellularity and hyperplasia in all airways studied and a progressive remodeling present in the terminal bronchioles. Our findings are consistent with the notion that the cumulative distal airway lesion is at least in part the result of a depressed cell proliferative response to injury in these airways. This depressed cell proliferative response may be in part the result of diminished neutrophil inflammation and/or release of mitogenic neuropeptides in response to ozone-induced injury.