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

Edward S Schelegle, William F. Walby, Mario F. Alfaro, Viviana J. Wong, Lei Putney, Mary Y. Stovall, Anja Sterner-Kock, Dallas M. Hyde, Charles Plopper

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)127-142
Number of pages16
JournalToxicology and Applied Pharmacology
Volume186
Issue number3
DOIs
StatePublished - Feb 1 2003

Fingerprint

Ozone
Substance P
Inhalation
Rats
Repair
Wounds and Injuries
Inflammation
Neutrophils
Cell proliferation
Bromodeoxyuridine
Neuropeptides
Physiological Adaptation
Bronchioles
Labels
Hyperplasia
Respiration
Air
Cell Proliferation

Keywords

  • Adaptation
  • Airway injury
  • Episodic exposure
  • Ozone
  • Repair
  • Substance P

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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

In: Toxicology and Applied Pharmacology, Vol. 186, No. 3, 01.02.2003, p. 127-142.

Research output: Contribution to journalArticle

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. / Repeated episodes of ozone inhalation attenuates airway injury/repair and release of substance P, but not adaptation. In: Toxicology and Applied Pharmacology. 2003 ; Vol. 186, No. 3. pp. 127-142.
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