Effects of Instilled Fibrogenic Particles on the Clonal Growth of Murine Pulmonary Alveolar Macrophages

Murine pulmonary alveolar macrophages (PAM) form macrophage colonies in vitro with colony-stimulating factors, which stimulate the clonal growth of radioresistant alveolar colony-forming cells (AL-CFC). The toxic effects of fibrogenic mineral dust particles on AL-CFC were investigated after intratracheal instillation into mice. Exposure to either crocidolite asbestos or silica (Min-u-sil) induced a significant depletion of AL-CFC as well as a decrease in PAM recovery compared to either untreated or titanium dioxide-exposed animals. Such effects were also noted with different doses (50-200μg/animal) of instilled particles. The plating efficiency of AL-CFC was depleted in PAM exposed to fibrogenic particles in vitro, but not when exposed to nonfibrogenic titanium dioxide particles. These results indicate the toxic effects of fibrogenic dust particles on the clonal growth of PAM, cells which play a role in the clearance of inhaled particles from the lung and in subsequent pathologic processes.