The Regulation of Lung Fibroblast Proliferation by Alveolar Macrophages in Experimental Silicosis1–3

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Abstract
To determine if macrophages regulate the numbers of fibroblasts in the silicotic lung, we exposed macrophages to quartz particles in vitro and in vivo and determined if the secretory products from these cells influenced the proliferation of cultured lung fibroblasts. Macrophages were recovered by lavage from the lungs of normal guinea pigs. Monolayers of these cells were exposed to sized quartz particles for 2 h. Macrophages were exposed to silica in vivo by the intratracheal injection of quartz particles. Macrophages were recovered from the silicotic guinea pigs 2,14, 42, and 180 days after injection. Monolayers of these cells were also cultured for 2 h in the absence of a stimulus. Fibroblasts were derived from expiants of the lungs of young guinea pigs. The effect of supernatants from the macrophage cultures on the proliferation of fibroblasts in vitro was determined in all experiments by measuring the incorporation of tritiated thymidine, and in some cases by direct cell counts. Macrophages exposed to quartz in vitro or for a short time (2 days) in vivo inhibited the proliferation of lung fibroblasts. In contrast, macrophages exposed in vivo for 42 and 180 days enhanced the proliferation of fibroblasts. These results suggest that alveolar macrophages from guinea pigs elaborate factors with opposing effects on the growth of fibroblasts and that the duration of exposure to silica is an important determinant of the predominant effect. These results also lend support to the notion that alveolar macrophages regulate the number of fibroblasts in the normal and the diseased lung.