Abstract
Toxicity of fibrogenic asbestos and silica particles on the in vitro colony-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 substances. Intratracheal instillation of crocidolite asbestos or Min-u-sil silica particles into mice induced significant and persistent reduction of alveolar macrophage colony-forming cells (AM-CFC) during the period of 1 to 6 months after treatments as compared to untreated control or groups of mice administered with nonfibrogenic TiO2 particles. Total numbers of PAM recovered by bron-choalveolar lavage, however, were not significantly different from the controls after asbestos or silica instillation. Instead, inflammatory exudation of polymorphonuclear leukocytes, lymphocytes, and monocytes significantly increased in the groups of asbestos- or silica-instilled animals, but not in TiO2-instilled mice. These data suggest that instilled fibrogenic particles have a cytotoxic effect on the proliferation and differentiation of PAM, while total PAM population could be maintained by recruitments of mononuclear phagocytes (monocytes) following inflammation or chemotactic events.