Ultrastructural study of bleomycin-induced pulmonary changes in mice

Abstract

The pulmonary changes produced in mice given bleomycin [a widely used antineoplastic drug] i.p. (twice weekly for 4 wk, total dose 240 mg/kg) were examined by light microscopy and EM. Bleomycin damaged the pulmonary vessels and produced type I pneumocyte necrosis, resulting in non-uniform pulmonary fibrosis. The sequence of events leading to pulmonary fibrosis were divided into 3 phases: First, a focal perivascular lesion consisting of interstitial edema with plasma cell and lymphocyte infiltration. The 2nd proliferative phase was characterized by type I pneumocyte necrosis, intra-alveolar fibrin deposition, an increase in the numbers of type II pneumocytes and fibroblasts and an overall decrease in the alveolar diameter. The 3rd phase consisted of organization, with intra-alveolar and interstitial collagen formation and the elastin synthesis. These phases, although occurring sequentially, did not bear a constant time relationship to the dosage schedule, for new early focal lesions continued to appear throughout the period of the experiment. These ultrastructural changes were not specific for bleomycin, but represent a general reaction of the lung to injury. The exact mechanism whereby bleomycin produced the lung damage has yet to be ascertained.