ACUTE RESPIRATORY BRONCHIOLITIS - ULTRASTRUCTURAL AND AUTORADIOGRAPHIC STUDY OF EPITHELIAL-CELL INJURY AND RENEWAL IN RHESUS-MONKEYS EXPOSED TO OZONE

Abstract

The pathogenesis of acute respiratory bronchiolitis was examined in rhesus monkeys exposed to 0.8 ppm ozone for 4-50 h. Epithelial injury and renewal was qualitatively and quantitatively characterized by correlated techniques of scanning and transmission electron microscopy and by light-microscopic autoradiography following labeling with tritiated thymidine. Extensive degeneration and necrosis of Type 1 epithelial cells occurred on the respiratory bronchiolar wall during the initial 4-12 h of exposure. Increased numbers of labeled epithelial cells were present in this region after 18 h of exposure, and the highest labeling index (18%) was measured after 50 h of exposure. Most (67-80%) of the labeled cells and all the mitotic epithelial cells (22) observed ultrastructurally were cuboidal bronchiolar epithelial cells. Of the labeled epithelial cells, 20-33% were Type 2 epithelial cells. After 50 h of exposure, the respiratory bronchiolar epithelium was hyperplastic. The predominant inflammatory cell in respiratory bronchiolar exudate was the alveolar macrophage. Monkeys that were exposed for 50 h and allowed to recover in unozonized air for 7 days had incomplete resolution of respiratory bronchiolar epithelial hyperplasia. Type 1 epithelial cells lining respiratory bronchioles are probably the cell type most sensitive to injury. Cuboidal bronchiolar epithelial cells and Type 2 epithelial cells may function as stem cells in epithelial renewal.