Pulmonary responses to bleomycin-induced injury: an immunomorphologic and electron microscopic study

Intratracheal injection of a small dose of bleomycin in rats induced early alveolar epithelial cell injury and a pneumonitis which subsequently evolved to pulmonary fibrosis. Hydropic degeneration of type I pneumocytes was apparent at 3 days after treatment. Marked interstitial and intra-alveolar pneumonitis developed at 7 days after treatment and was accompanied by hypertrophy and hyperplasia of type II pneumocytes. The inflammatory cell population consisted predominantly of cells with the morphology of large lymphocytes together with a number of eosinophils. Examination by immunoperoxidase and histochemical staining of frozen sections revealed that the lymphoid cells stained positively with the monoclonal antibodies W3/13 and W3/25 but not with other markers. Thus these cells appeared to be helper T lymphocytes. The later development of interstitial fibrosis was accompanied by alveolar microcollapse which contributed to the thickening of alveolar septa observed by light microscopy. The possible role of immunologic and other mechanisms in the pathogenesis of bleomycin-induced pulmonary fibrosis is discussed.