RESPONSE OF MACAQUE BRONCHIOLAR EPITHELIUM TO AMBIENT CONCENTRATIONS OF OZONE

Recently, we reported that exposure to ambient concentrations of ozone , near the U.S. National Ambient Air Quality Standard (0.12 ppm), indu ced significant nasal epithelial lesions in a non-human primate, the b onnet monkey. The present study defines the effects of ambient concent rations of ozone on the surface epithelium lining respiratory bronchio les and on the underlying bronchiolar interstitium in these same monke ys. Bonnet monkeys were exposed to filtered air or to 0.15 or 0.30 ppm ozone 8 hours/day for 6 or 90 days. At the end of exposures, monkeys were anesthetized and killed by exsanguination. Micro-dissected bronch iolar airways of infusion-fixed lungs were evaluated morphometrically by light microscopy and quantitatively by scanning and transmission el ectron microscopy for ozone-induced epithelial changes. Hyperplasia of nonciliated, cuboidal epithelial cells and intraluminal accumulation of macrophages characterized ozone-induced lesions in respiratory bron chioles. There were no significant differences in epithelial thickness or cell numbers among ozone-exposed groups. Ozone-exposed epithelium was composed of 80% cuboidal and 20% squamous cells compared with 40% cuboidal and 60% squamous cells in filtered air controls. In addition, the arithmetic mean thickness of the surface epithelium, a measure of tissue mass per unit area of basal lamina, was significantly increase d in an of the ozone-exposed groups. The number of cuboidal epithelial cells per surface area of basal lamina was increased above control va lues by 780% after 6 days exposure to 0. 15 ppm, 777% after 90 days to 0.15 ppm, and 996% after 90 days exposure to 0.30 ppm. There was also a significant ozone-induced increase in the thickness of the bronchio lar interstitium that was due to an increase in both cellular and acel lular components. These results demonstrate that exposure to low ambie nt concentrations of ozone, near the current. National Ambient Air Qua lity Standard, induces pulmonary lesions in primates. The alterations do not appear to be concentration- or time-dependent, suggesting that the current National Ambient Air Quality Standard may be at or above t he threshold for deep lung injury in primates.