DOSE-DEPENDENT TOLERANCE TO OZONE .3. ELEVATION OF INTRACELLULAR CLARA CELL 10-KDA PROTEIN IN CENTRAL ACINI OF RATS EXPOSED FOR 20 MONTHS

Understanding factors that promote pulmonary tolerance to long-term ox idant injury is essential to evaluating health risks in humans. One su ch factor may be Clara cell 10-kDa protein (CC10), a protein secreted by nonciliated cells in distal conducting airways thought to have an a nti-inflammatory action against inhaled xenobiotics. Using standard im munohistochemical techniques and laser scanning confocal microscopy, w e assessed changes in CC10 abundance in the centriacinar region of the rat following 20 months' exposure to 0.12 and 1.00 ppm ozone. Three z ones of reflectance intensity (high, medium, and low), directly relate d to CC10 density, were used to distinguish between the two major subc ellular compartments where CC10 is distributed: granules and endoplasm ic reticulum. Low levels of ozone (0.12 ppm) had no significant effect on the cellular distribution or abundance of CC10 in nonciliated epit helium in the centriacinar region. In contrast, 1.00 ppm ozone not onl y elevated cellular volume of granule-based CC10, but also elevated th e protein's concentration within the granules and increased the number of granules per cell profile. The proportion of nonciliated cells in terminal bronchioles increased significantly at the expense of ciliate d cells. This combination of factors led to a threefold increase in CC 10 stored per unit surface area of epithelium in terminal bronchioles. The nonciliated cells in ozone-induced respiratory bronchioles contai ned a distribution of CC10 similar to that of bronchiolar nonciliated cells in control animals. We conclude that ozone-induced tolerance may be related to the increased abundance and wider distribution of CC10 in central acini of rats following long-term ozone exposure. (C) 1994 Academic Press,Inc.