Effect of Chronic Daily Ozone Exposure on Clara Cell Secretory Protein mRNA Expression in the Adult Rat Lung

Abstract

Short-term exposure to the air pollutant ozone results in severe injury to the nares, trachea, and centriacinus. Long-term exposure, however, leads to a state of tolerance that is characterized by remodeling in the centriacinar airways and markedly reduced cell necrosis and inflammation. This remodeling consists of hypertrophy and hyperplasia of Clara cells with a 2- to 5-fold increase in the intracellular content of the major protein synthesized by the Clara cell, Clara cell secretory protein (CCSP). Previous in vitro studies suggest that CCSP may moderate inflammation and bind reactive cytotoxicants. This study tested whether acute and chronic exposure to ozone alters the normal level of expression of the CCSP gene. Rats were exposed to ozone, 1 ppm, 8 h nightly, for up to 90 days. Immunohistochemistry demonstrated repopulation of the alveolar ducts with CCSP positive Clara cells and an increase in the intensity of immunoreactive CCSP within Clara cells. The results showed that (1) CCSP mRNA expression, GAPDH, and β-actin do not change as a result of ozone injury, (2) mRNA levels are more variable as a result of ozone injury, and (3) CCSP mRNA expression increases with age.