Activation of calcitonin gene-related peptide receptor during ozone inhalation contributes to airway epithelial injury and repair.
The authors investigated the importance of the neuropeptide, calcitonin gene-related peptide (CGRP), in epithelial injury, repair, and neutrophil emigration after ozone exposure. Wistar rats were administered either a CGRP-receptor antagonist (CGRP(8-37)) or saline and exposed to 8 hours of 1-ppm ozone or filtered air with an 8-hour postexposure period. Immediately after exposure, ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, airway dissected lung lobes were stained for 5'-bromo-2'-deoxyuridine, a marker of epithelial proliferation. Positive epithelial cells were quantified in specific airway generations. Rats treated with CGRP(8-37) had significantly reduced epithelial injury in terminal bronchioles and reduced epithelial proliferation in proximal airways and terminal bronchioles. Bronchoalveolar lavage and sections of terminal bronchioles showed no significant difference in the number of neutrophils emigrating into airways in CGRP(8-37)-treated rats. The airway epithelial cell line, HBE-1, showed no difference in the number of oxidant stress positive cells during exposure to hydrogen peroxide and a range of CGRP(8-37) doses, demonstrating no antioxidant effect of CGRP(8-37). We conclude that activation of CGRP receptors during ozone inhalation contributes to airway epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.
Oslund
Karen L
KL
The Center for Comparative Respiratory Biology and Medicine, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Hyde
Dallas M
DM
Putney
Leialoha F
LF
Alfaro
Mario F
MF
Walby
William F
WF
Tyler
Nancy K
NK
Schelegle
Edward S
ES
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D055745:Bronchioles / Q000187:drug effects / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010126:Ozone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D056152:Respiratory Rate / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; C058636:calcitonin gene-related peptide (8-37); D010126:Ozone; D015740:Calcitonin Gene-Related Peptide