Abstract
The influence of coal dust on the alveolar type II pulmonary epithelium may involve direct dust-type II cell interactions or indirect effects mediated through production of cytokines or other products by nearby alveolar macrophages. Previous studies showed an effect of anthracite coal dust (PSOC 867) in modulating synthesis of extracellular matrix components by the type II cell in a dose-dependent manner. The present study confirms those observations and suggests further indirect effects due to type II cell-alveolar macrophage interactions during dust exposure in vitro. Exposure of type II cells to 867 (750 μg/ml) altered synthesis of matrix proteins. Coculture of alveolar macrophages with type II cells did not change synthesis of extracellular matrix proteins by control pneumocytes, but significantly increased the response of the cells to 867. Tumor necrosis factor-α (TNF-α) was evaluated as a possible mediator of the latter macrophage effect. Exogenous TNF-α caused a modest dose-dependent stimulation of extracellular matrix protein synthesis in the presence of 867 on culture day 3, but had no stimulatory effect when dust was absent. The overall direct effects of TNF-α on protein synthesis were not, however, quantitatively consistent with a role for the cytokine in macrophage-mediated alterations in matrix protein synthesis. These observations support the premise that coal dust acts on the alveolar epithelium by both direct and indirect pathways. The latter may involve the action of dust on the alveolar macrophage to result in release of soluble modulators of type II cell matrix metabolism.