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Modulation of fibroblast activity by normal and silica-exposed alveolar macrophages
Abstract:
Silica-induced pulmonary fibrosis is thought to involve fibroblast stimulation by a product of alveolar macrophages (AM) but various cell culture systems have given conflicting results. Macrophage-fibroblast interactions are now studied using an homologous system in which supernatants of rat AM after incubation with silica, are tested on fibroblasts isolated from the same animals to assess the effects on cell proliferation and collagen production. Fibroblast growth varied with initial seeding density and changes induced by AM supernatants varied depending on the proliferative rate. Normal AM supernatants inhibited [3H]-thymidine incorporation into fibroblasts, especially in more rapidly dividing cells. Supernatants of silica-treated AMs also inhibited division of rapidly growing fibroblasts, whereas the same material stimulated growth of slowly dividing cells. Collagen synthesis increased with the length of time that fibroblasts were confluent and was inhibited by control AM supernatants. Silica-treated AM supernatants increased collagen production by fibroblasts confluent for 3 days, whereas the same supernatants inhibited collagen synthesis by cells confluent for at least 8 days. The observation that a factor derived from silica-exposed AM first stimulates them inhibits fibrogenesis, indicates a modulation of the normal macrophage-fibroblast control system. This suggests that other factors may be required in vivo to shift this cellular balance towards the fibrotic process.
Insights
Silica exposure affects macrophage-fibroblast interactions. Macrophage products initially inhibit, then stimulate fibroblast growth and collagen production, suggesting complex regulation in pulmonary fibrosis.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Toxicology
Background:
- Silica-induced pulmonary fibrosis involves alveolar macrophages (AM) and fibroblasts.
- Previous cell culture systems yielded conflicting results on macrophage-fibroblast interactions.
Purpose of the Study:
- To investigate macrophage-fibroblast interactions in silica-induced pulmonary fibrosis using a homologous rat system.
- To assess the effects of silica-treated AM supernatants on fibroblast proliferation and collagen production.
Main Methods:
- Supernatants from silica-treated rat AM were applied to rat fibroblasts.
- Assessed fibroblast proliferation (thymidine incorporation) and collagen synthesis.
- Varied fibroblast seeding density and confluency duration.
Main Results:
- AM supernatants modulated fibroblast proliferation based on cell growth rate.
- Silica-AM supernatants inhibited rapidly growing fibroblasts but stimulated slowly growing ones.
- Collagen synthesis was differentially affected by silica-AM supernatants based on fibroblast confluency duration.
Conclusions:
- Silica-exposed AM products modulate the normal macrophage-fibroblast control system.
- Initial stimulation followed by inhibition of fibrogenesis suggests complex regulation.
- Additional factors may be necessary in vivo to promote fibrotic processes.