Am. J. Respir. Crit. Care Med., Volume 157, Number 3, March 1998, 970-977

Proliferation of Airway Epithelium After Ozone Exposure
Effect of Apocynin and Dexamethasone

MICHAEL SALMON, HIROSHI KOTO, OONAGH T. LYNCH, EL-BDAOUI HADDAD, NICHOLAS J. LAMB, GREGORY J. QUINLAN, PETER J. BARNES, and K. FAN CHUNG

Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom

Ozone is an environmental pollutant with potent oxidizing properties. We investigated whether exposure to ozone-induced cell proliferation in the lungs of rats, and determined the effect of an antioxidant and of a glucocorticosteroid in Brown-Norway (BN) rats. Following single ozone exposure (0.5, 1.0, or 3.0 ppm for 6 h), proliferating cell nuclear antigen (PCNA) expression, as determined with immunohistochemistry, was significantly increased in the bronchial epithelium and alveolar epithelium as compared with controls exposed to filtered air with a maximal effect at 24 to 48 h (p < 0.001). Apocynin (5 mg/kg, orally), a reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, reduced the PCNA index in bronchial epithelium induced by ozone (3 ppm, 6 h) from 11.5 ± 1.3% (percent of nuclear cells expressing PCNA) to 4.4 ± 1.3% (mean ± SEM; p < 0.05). Dexamethasone (3 mg/kg, intraperitoneally) also reduced the PCNA index in bronchial epithelium, from 19.2 ± 2.3% to 10.9 ± 2.6% (p < 0.05). Dexamethasone but not apocynin inhibited ozone- induced neutrophil influx. Rats exposed repeatedly to ozone (3.0 ppm, 3 h, on three occasions 48 h apart) expressed a lower PCNA index in bronchial epithelium than did rats exposed only once at 1.9 ± 0.7% versus 6.0 ± 0.9%, respectively (p < 0.05). The proliferative epithelial response following a single exposure to ozone is modulated through oxidative and inflammatory mechanisms probably involving neutrophils.

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