Mast cells contribute to ozone-induced epithelial damage and proliferation in the nasal and bronchial airways of mice. Longphre, Malinda, Liu-Yi Zhang, Jack R. Harkema, and Steven R. Kleeberger. Department of Environmental Health Sciences, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205 and Department of Pathology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824-1314
APStracts 2:0531A, 1995.
Ozone (O3) exposure produces inflammation in the airways of humans and animal models. However, the mechanism by which O3 affects these changes is uncertain. Mast cells are strategically located below the epithelium of the airways and are capable of releasing a number of pro-inflammatory mediators. We tested the hypothesis that mast cells contribute to inflammation, epithelial sloughing, and epithelial proliferation in the nasal and terminal bronchiolar murine airways following O3 exposure. Mast cell sufficient (+/+), mast cell deficient (W/Wv), and mast cell repleted (BMT W/Wv) mice were exposed to 2 ppm O3 or filtered air for 3h. Nasal (NL) and bronchoalveolar (BAL) lavage fluids were collected 6h and 24h after exposure. Differential cell counts and protein content of the lavage fluids were used as indicators of inflammation and permeability changes in the airways. O3-induced epithelial injury was assessed by light microscopy and O3-induced DNA synthesis in airway epithelium was estimated using a bromodeoxyuridine (BrdU) labeling index in the nasal and terminal bronchiolar epithelia. Relative to air controls, O3 caused significant increases in inflammation, epithelial injury, and epithelial DNA synthesis in +/+ mice. There was no significant effect of O3 exposure on any measured parameter in the W/Wv mice. To further assess the role of mast cells in O3-induced epithelial damage, mast cells were restored in W/Wv mice by bone marrow transplantation (BMT) from +/+ congeners. Relative to sham -transplanted W/Wv mice, O3 caused significant increases in epithelial damage and DNA synthesis as well as inflammatory indicators in BMT W/Wv mice. These observations are consistent with the hypothesis that mast cells significantly modulate the inflammatory and proliferative responses of the murine airways to O3. 

Received 7 August 1995; accepted in final form 17 November 1995.
APS Manuscript Number A864-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95