BACKGROUND: The proliferative response of type II cells is an important event following silica-induced lung injury. Alveolar macrophages, when activated by fibrogenic agents, secrete various biological mediators which affect cell growth. METHODS: Human alveolar macrophages from normal volunteers were incubated in serum-free medium or in the presence of increasing concentrations of silica. Alveolar macrophage conditioned media were diluted and added to type II cell cultures for proliferation studies. Purified type II pneumocytes were isolated from fetal rat lungs for bioassays. Growth factor activities were partially characterised by size exclusion chromatography. Each fractionated mitogenic peak was preincubated with monoclonal antibody against platelet derived growth factor (PDGF) or antisera against insulin-like growth factor 1 (IGF-1) or fibroblast derived growth factor (FGF) in order to study the nature of each activity. RESULTS: Conditioned media from alveolar macrophages exposed to silica induced an increase in type II cell DNA synthesis and cell number over that seen when type II cells were incubated with unstimulated alveolar macrophage supernatants. Size exclusion of alveolar macrophage supernatants exposed to silica showed four peaks of type II cell stimulating activity with apparent molecular weights of 38, 22, 16, and 8 kDa. Anti-PDGF antibody significantly reduced the activity of the first and second peaks, antiserum against IGF-1 partially reduced the activity of the first and fourth peaks, and antiserum against FGF reduced only the third peak of activity. CONCLUSIONS: Human alveolar macrophages exposed to silica in vitro release mitogens for type II pneumocytes including PDGF-like, IGF-1-like, and FGF-like molecules. These agents are likely to be involved in the epithelial repair and type II cell hyperplasia observed in silicosis.
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