PROLIFERATION OF AIRWAY EPITHELIUM AFTER OZONE EXPOSURE - EFFECT OF APOCYNIN AND DEXAMETHASONE

Ozone is an environmental pollutant with potent oxidizing properties. We investigated whether exposure to ozone-induced cell proliferation i n the lungs of rats, and determined the effect of an antioxidant and o f a glucocorticosteroid in Brown-Norway (BN) rats. Following single oz one exposure (0.5, 1.0, or 3.0 ppm for 6 h), proliferating cell nuclea r antigen (PCNA) expression, as determined with immunohistochemistry, was significantly increased in the bronchial epithelium and alveolar e pithelium as compared with controls exposed to filtered air with a max imal effect at 24 to 48 h (p < 0.001):Apocynin (5 mg/kg, orally), a re duced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhi bitor, 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 3 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 n ot apocynin inhibited ozone-induced neutrophil influx. Rats exposed re peatedly to ozone (3.0 ppm, 3 h, on three occasions 48 h apart) expres sed a lower PCNA index in bronchial epithelium than did rats exposed o nly 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 proba bly involving neutrophils.