Ozone-induced Adaptive and Reactive Cellular Changes in Respiratory Bronchioles of Bonnet Monkeys

Abstract

To characterize the response of respiratory bronchioles (RBs) to chronic high ambient levels of ozone, bonnet monkeys were exposed for 90 days to 0, 0.4, or 0.64 ppm ozone (UV photometric standard; 3 monkeys/exposure). Morphologic changes in respiratory bronchiolar epithelium and interstitium were evaluated quantitatively at both the light and transmission electron microscopic levels. Significant changes in respiratory bronchioles following exposure included: (1) a thicker wall and a narrower lumen, (2) a thicker epithelial compartment and a much thicker interstitial compartment, (3) shifts in epithelial cell populations with many more nonciliated bronchiolar epithelial cells and fewer squamous type I epithelial cells, (4) larger nonciliated bronchiolar epithelial cells with a larger compliment of cellular organelles associated with protein synthesis, (5) greater amounts of both interstitial fibers and amorphous ground substance, (6) greater numbers of interstitial smooth muscle cells per epithelial basal lamina surface area, and (7) greater volumes of interstitial smooth muscle, macrophages, mast cells, and neutrophils per epithelial basal lamina surface area. These observations imply that chronic ozone exposure causes a concentration-dependent reactive peribronchiolar inflammatory response and an adaptive response consisting of hypertrophy and hyperplasia of the nonciliated bronchiolar cell.