Apoptosis-like changes in the lungs induced by cyclophosphamide and papain. I. An ultrastructural study.

An ultrastructural study was made to analyze the structural and cellular features of the pulmonary lesions produced in Wistar rats by the administration of cyclophosphamide (CP) and/or papain (P). Combined administration of cyclophosphamide and papain caused severe damage to lung tissue including necrosis, particularly to alveolar epithelial and endothelial cells. Some of the damaged type II cells showed nuclear and cytoplasmic features that are considered indicative of apoptosis. Apoptosis-like changes were also observed in endothelial and mesenchymal cells in the interstitium of interalveolar septa. Phagocytosis of apoptotic bodies by macrophages was found too. Apoptosis-like changes were not revealed in those areas of lung tissue where fibroplasia processes prevailed. Nor were they observed in the animals receiving papain only. Occasionally apoptosis-like changes were found in type II cells and in endothelial cells in rats given cyclophosphamide only. The results obtained also suggest the possibility of active participation of type II alveolar epithelial cells in the fibroplasia process in the course of lung rebuilding in acute lung tissue damage induced with simultaneous administration of cyclophosphamide and papain.