Ultrastructural study of bleomycin-induced pulmonary changes in mice.

The pulmonary changes produced in mice given bleomycin intraperitoneally (twice weekly for 4 weeks, total dose 240 mg/kg) were examined by light and electron microscopy. 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 may be arbitrarily divided into three phases: firstly, a focal perivascular lesion consisting of interstitial oedema with plasma cell and lymphocyte infiltration; followed by the middle proliferative phase characterised 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 third phase consisted of organisation, with intra-alveolar and interstitial collagen formation and the synthesis of elastin. 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 are not specific for bleomycin, but represent a general reaction of the lung to injury. The exact mechanism whereby bleomycin produces the lung damage has yet to be ascertained.