Two hypolipidemic peroxisome proliferators increase the number of lamellar bodies in alveolar cells type II of the rat lung.

Male rats treated with either clofibrate or nafenopin, two peroxisome proliferating compounds with potent hypolipidemic properties, show identical structural changes in their lungs. In both cases, two types of lung cells were affected by these agents: (i) the alveolar epithelial cells type II and (ii) the intraalveolar macrophages. These lung cells are known to be involved in the metabolism of the pulmonary surfactant which serves to reduce the surface tension within alveoli. The size of the alveolar cells type II was conspicuously increased in the treated lungs. Compared to controls, intraalveolar macrophages apparently were slightly more numerous. Their enlarged cytoplasm was strongly vacuolated. The osmiophilic lamellar bodies within alveolar cells type II represent the intracellular presecretory pulmonary surfactant. Their number per individual alveolar cell type II was estimated by means of light microscopic morphometry on Epon-embedded semithin sections. Compared to control lungs, the number was increased by about 30% in rats treated with clofibrate (11.4 +/- 0.5 lamellar inclusions in the control cells; P less than 0.001). The increase in the number of lamellar bodies per type II cell was close to 60% in animals fed the nafenopin diet. In contrast the frequency of alveolar cells type II, estimated per area of lung tissue, remained unchanged. These results demonstrate that clofibrate and nafenopin, two drugs with hypolipidemic properties, cause identical structural changes in the rodent lung. It is concluded from these data that (i) the morphological changes observed in the surfactant metabolizing cells represent a specific action of hypolipidemic agents at the lungs and (ii) hypolipidemic peroxisome proliferators influence the metabolism of the pulmonary surfactant.