Repeated episodes of ozone inhalation attenuates airway injury/repair and release of substance P, but not adaptation.
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.
Schelegle
Edward S
ES
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. esschelegle@ucdavis.edu
Walby
William F
WF
Alfaro
Mario F
MF
Wong
Viviana J
VJ
Putney
Lei
L
Stovall
Mary Y
MY
Sterner-Kock
Anja
A
Hyde
Dallas M
DM
Plopper
Charles G
CG
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
D010083:Oxidants, Photochemical; D013373:Substance P; D010126:Ozone