Activation of neurokinin-1 receptors during ozone inhalation contributes to epithelial injury and repair

Karen L. Oslund, Dallas M. Hyde, Leialoha F. Putney, Mario F. Alfaro, William F. Walby, Nancy K. Tyler, Edward S Schelegle

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We investigated the importance of neurokinin (NK)-1 receptors in epithelial injury and repair and neutrophil function. Conscious Wistar rats were exposed to 1 ppm ozone or filtered air for 8 hours, followed by an 8-hour postexposure period. Before exposure, we administered either the NK-1 receptor antagonist, SR140333, or saline as a control. Ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, whole mounts of airway dissected lung lobes were immunostained for 5-bromo-2′- deoxyuridine, a marker of epithelial proliferation. Both ethidium homodimer and 5-bromo-2′-deoxyuridine-positive epithelial cells were quantified in specific airway generations. Rats treated with the NK-1 receptor antagonist had significantly reduced epithelial injury and epithelial proliferation compared with control rats. Sections of terminal bronchioles showed no significant difference in the number of neutrophils in airways between groups. In addition, staining ozone-exposed lung sections for active caspase3 showed no apoptotic cells, but ethidium-positive cells colocalized with the orphan nuclear receptor, Nur77, a marker of nonapoptotic, programmed cell death mediated by the NK-1 receptor. An immortalized human airway epithelial cell line, human bronchial epithelial-1, showed no significant difference in the number of oxidant stress-positive cells during exposure to hydrogen peroxide and a range of SR140333 doses, demonstrating no antioxidant effect of the receptor antagonist. We conclude that activation of the NK-1 receptor during acute ozone inhalation contributes to epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.

Original languageEnglish (US)
Pages (from-to)279-288
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume39
Issue number3
DOIs
StatePublished - Sep 1 2008

Fingerprint

Neurokinin-1 Receptors
Ozone
Neurokinin-1 Receptor Antagonists
Inhalation
Neutrophils
Repair
Epithelial Cells
Chemical activation
Bromodeoxyuridine
Lung
Nuclear Receptor Subfamily 4, Group A, Member 1
Wounds and Injuries
Bronchioles
Ethidium
Emigration and Immigration
Cells
Oxidants
Hydrogen Peroxide
Wistar Rats
Rats

Keywords

  • Cell proliferation
  • Neurokinin-1 receptor
  • Neutrophil emigration
  • Nonapoptotic programmed cell death
  • Oxidant airway injury

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Activation of neurokinin-1 receptors during ozone inhalation contributes to epithelial injury and repair. / Oslund, Karen L.; Hyde, Dallas M.; Putney, Leialoha F.; Alfaro, Mario F.; Walby, William F.; Tyler, Nancy K.; Schelegle, Edward S.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 39, No. 3, 01.09.2008, p. 279-288.

Research output: Contribution to journalArticle

Oslund, Karen L. ; Hyde, Dallas M. ; Putney, Leialoha F. ; Alfaro, Mario F. ; Walby, William F. ; Tyler, Nancy K. ; Schelegle, Edward S. / Activation of neurokinin-1 receptors during ozone inhalation contributes to epithelial injury and repair. In: American Journal of Respiratory Cell and Molecular Biology. 2008 ; Vol. 39, No. 3. pp. 279-288.
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