Pulmonary lesions induced by 3-methylindole in mice

The morphogenesis of pulmonary lesions and associated edema induced by the pulmonary toxicant 3-methylindole (3-MI) was studied by combined light and transmission electron microscopy. Weanling male CD-1 mice received 3-MI dissolved in corn oil by intraperitoneal injection and were studied at intervals from 2 to 360 hours after treatment. Interstitial edema was observed as early as 2 hours and was associated with focal cytoplasmic swelling and membrane alterations in both capillary endothelial cells and Type I alveolar epithelial cells and with sequestration of neutrophils. Cell swelling, cytoplasmic fragmentation, and necrosis of Type I epithelial cells was most severe at 24-48 hours after treatment. Multifocal hypertrophy and hyperplasia of Type II alveolar epithelial cells was observed at 24-96 hours after treatment. Platelet aggregation and aggregates of fibrin were frequently observed in capillaries and small arteries and veins as early as 4 hours and as late as 48 hours after treatment. In airways, the nonciliated bronchiolar epithelial (Clara) cell was the predominant cell affected. Initial lesions in nonciliated cells consisted of loss of microvilli and secretory granules followed by marked swelling of the endoplasmic reticulum and mitochondria. Necrosis of cells lining airways was most pronounced at 24-48 hours after treatment. By 144 hours after administration, pulmonary repair was complete. It is concluded that the mouse is a useful model of 3-MI-induced pulmonary injury and that damage to both Type I alveolar epithelial cells and capillary endothelial cells is important in the pathogenesis of 3-MI-induced pulmonary edema.