Morphologic alteration of mouse Clara cells induced by glycerol: ultrastructural and morphometric studies

In our studies on activation of the Clara cell by biological substances and its relationship to pulmonary carcinogenesis, we found that large doses of glycerol induced drastic morphologic changes selectively in the Clara cell among distal airway epithelial cells in ddY mice. Subcutaneous injection of glycerol (7.2 g/Kg body weight) caused cytoplasmic edema with disruption of endoplasmic reticulum membranes at 1 and 3 hours, followed by hyperplasia of smooth endoplasmic reticulum (SER) at 12 and 24 hours. Concentric lamination of SER was observed at 48 and 96 hours. Oral administration of 5% glycerol in drinking water for 2 to 8 weeks induced more conspicuous hyperplasia and hypertrophy of SER in the Clara cells. Electron microscopic morphometry revealed a 3-fold increase in the profile area of SER in the Clara cells of the animals at 2 and 8 weeks. Both the profile area and the number of secretory granules increased significantly at 2 and 8 weeks, and those of mitochondria tended to increase with time of glycerol treatment. In both experiments, the mitochondria of the Clara cells exhibited marked elongation and distortion of the contour associated with appearance of prominent cristae. These results suggest that large doses of glycerol induce marked alteration in the functional activity of the mouse Clara cell.