title: Repeated episodes of ozone inhalation attenuates airway injury/repair and release of substance P, but not adaptation.
abstract: 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.
authors.affiliation: Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. esschelegle@ucdavis.edu
authors.forename: Edward S
authors.initials: ES
authors.lastname: Schelegle
authors.forename: William F
authors.initials: WF
authors.lastname: Walby
authors.forename: Mario F
authors.initials: MF
authors.lastname: Alfaro
authors.forename: Viviana J
authors.initials: VJ
authors.lastname: Wong
authors.forename: Lei
authors.initials: L
authors.lastname: Putney
authors.forename: Mary Y
authors.initials: MY
authors.lastname: Stovall
authors.forename: Anja
authors.initials: A
authors.lastname: Sterner-Kock
authors.forename: Dallas M
authors.initials: DM
authors.lastname: Hyde
authors.forename: Charles G
authors.initials: CG
authors.lastname: Plopper
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018893:Bronchoalveolar Lavage; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016015:Logistic Models; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000633:toxicity*; D010126:Ozone / Q000008:administration & dosage* / Q000633:toxicity*; D051381:Rats; D012119:Respiration / Q000187:drug effects; D013373:Substance P / Q000378:metabolism*; D013997:Time Factors; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
chemical_list: D010083:Oxidants, Photochemical; D013373:Substance P; D010126:Ozone