Cytochrome-P450 2B1 Immunoreactivity in Bronchiolar and Alveolar Epithelial Cells after Exposure of Rats to Ozone

Abstract

Pulmonary cytochrome P450 (P450) plays an important role in the metabolism of xenobiotics. We have previously demonstrated that exposure to ozone (O3), a major oxidant of photo-chemical smog, increases P450 content and xenobiotic metabolizing activities in the rat lung. Therefore, it is conceivable that O3 exposures modify the pattern and potency of xenobiotic metabolism. The aim of this study is to examine the effect of O3 exposure on localization of P450 in the lung. After exposure of rats to 0.4 ppm O3 for 14 days, the concentration of P450 2B1, the main isozyme of P450 in the lung, increased to 214% of the control value. By immunohistochemical analyses, O3 exposure caused hypertrophy and hyperplasia of P450 2B1-positive nonciliated bronchiolar epithelial (Clara) cells, showing an increase in the cell number to 128% of the control level. At the proximal alveoli, O3 exposure induced hypertrophic epithelial cells that presented immunoreactivity to P450 2B1 the morphological characteristics of both type 1 and type 2 cells. These hypertrophic cells had lamellar inclusion bodies, microvilli, and extended cytoplasm. Typical type 2 cells did not react with anti-P450 2B1 antibody even after O3 exposure. These data suggest that O3 exposure may activate the P450-mediated xenobiotic metabolism in the pulmonary epithelial cells, and that expression of P450 2B1 in the pulmonary epithelial cells might be regulated by the factors involved in the process of the differentiation from type 2 to type 1 cells.