Kinetics of intraparenchymal mononuclear cells in a murine model of pulmonary fibrosis induced by bleomycin

Bleomycin (BLM), an anti-tumor drug, has been observed to cause interstitial pneumonia followed by subsequent fibrosis. In order to elucidate the cellular mechanism in the fibrotic process, we examined inflammatory cells in the lungs of mice after intratracheal administration of BLM. Microscopic observation of May-Giemsa-stained cells demonstrated that the number of macrophages remained at the basal level as of day 3, then increased and peaked on days 7 to 14, while the number of lymphocytes increased as early as day 1, peaked on day 7, and then gradually decreased. In flow cytometric analysis, the numbers of both B and T cells, including both CD4+ and CD8+ T cells, showed a rapid increase after administration of BLM. The T cells were activated, as indicated by the induction of IL-2 receptor (IL-2R) and the augmented expression on their surface of leukocyte function associated antigen-1 (LFA-1), which has also been regarded as a T cell activation marker. In addition, marked accumulation of γ δ T cells was observed in the lungs of mice treated with BLM, although it has not been elucidated whether these cells were involved in the pathogenesis. These results suggest that the increase of intraparenchymal macrophages and lymphocytes and the activation of T cells are prerequisite for the development of pulmonary fibrosis.