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The regulation of lung fibroblast proliferation by alveolar macrophages in experimental silicosis
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 explants 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.
Insights
Alveolar macrophages influence lung fibroblast numbers differently based on silica exposure duration. Short-term exposure inhibits fibroblast proliferation, while long-term exposure enhances it, suggesting macrophages regulate fibroblast populations in lung disease.
Area of Science:
- Pulmonary immunology
- Cell biology
- Fibrosis research
Background:
- Alveolar macrophages play a role in lung homeostasis.
- Silicosis involves lung inflammation and fibrosis, characterized by fibroblast proliferation.
- The precise regulatory role of macrophages on fibroblasts in silicosis is not fully understood.
Purpose of the Study:
- To investigate whether alveolar macrophages regulate fibroblast numbers in silicotic lungs.
- To determine the effect of macrophage secretory products on lung fibroblast proliferation after silica exposure.
Main Methods:
- Guinea pig alveolar macrophages were exposed to quartz particles in vitro and in vivo.
- Macrophages were recovered at various time points after in vivo silica exposure (2, 42, 180 days).
- Supernatants from macrophage cultures were applied to cultured lung fibroblasts, and proliferation was assessed using tritiated thymidine incorporation and cell counts.
Main Results:
- Macrophages exposed to silica in vitro or for a short duration (2 days) in vivo inhibited lung fibroblast proliferation.
- Macrophages exposed in vivo for longer durations (42 and 180 days) enhanced fibroblast proliferation.
- These findings indicate silica-exposed macrophages release factors with opposing effects on fibroblast growth.
Conclusions:
- Alveolar macrophages from guinea pigs secrete factors that can either inhibit or enhance lung fibroblast proliferation.
- The duration of silica exposure is a critical factor determining the predominant effect of macrophages on fibroblast growth.
- These results support the role of alveolar macrophages in regulating fibroblast populations in both normal and diseased lungs, including silicosis.