Modulation of fibroblast activity by normal and silica-exposed alveolar macrophages.
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.
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects*; D011392:Proline / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D011919:Rats, Inbred Strains; D012822:Silicon Dioxide / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D012822:Silicon Dioxide; D003094:Collagen; D011392:Proline; D013936:Thymidine