CYTOTOXICITY OF FIBROGENIC ASBESTOS AND SILICA ON MURINE PULMONARY ALVEOLAR MACROPHAGE COLONY-FORMING CELLS

Toxicity of fibrogenic asbestos and silica particles on the in vitro c olony-forming capacity of murine pulmonary alveolar macrophages (PAM) was tested to elucidate the possibility that the proliferation or the maintenance of the PAM population could be affected by inhaled substan ces. Intratracheal instillation of crocidolite asbestos or Min-u-sil s ilica particles into mice induced significant and persistent reduction of alveolar macrophage colony-forming cells (AM-CFC) during the perio d of 1 to 6 months after treatments as compared to untreated control o r groups of mice administered with nonfibrogenic TiO2 particles. Total numbers of PAM recovered by bronchoalveolar lavage, however, were not significantly different from the controls after asbestos or silica in stillation. Instead, inflammatory exudation of polymorphonuclear leuko cytes, lymphocytes, and monocytes significantly increased in the group s of asbestos- or silica-instilled animals, but not in TiO2-instilled mice. These data suggest that instilled fibrogenic particles have a cy totoxic effect on the proliferation and differentiation of PAM, while total PAM population could be maintained by recruitments of mononuclea r phagocytes (monocytes) following inflammation or chemotactic events.