Excessive production of insulin-like growth factor-I by silicotic rat alveolar macrophages

The supernatant of silicotic rat alveolar macrophages can stimulate fibroblast growth. The present study demonstrates that this activity is mainly attributed to insulin-like growth factor-I. Partial purification of the supernatant of alveolar macrophages, which were from silica-exposed 5 to 6-week-old rats, revealed a protein peak (peak 5) eluted from a molecular-sieve HPLC column, corresponding to a MW of 6-9 kDa. Activity assay and radioimmunoassay indicated that this peak is more potent with regard to stimulation of fibroblast growth and has higher insulin-like growth factor-I immunoreactivity, but there was no detectable activity of interleukin-1 or tumor necrosis factor. Quantification of insulin-like growth factor-I also manifests elevated insulin-like growth factor-I levels in silicotic rat bronchoalveolar lavage fluids which tend to increase with prolongation of silica exposure in vivo, but no alteration in insulin-like growth factor-I level can be found in sera. These findings suggest that excessive production of insulin-like growth factor-I by alveolar macrophages locally may play a pivotal role in silica-induced pulmonary interstitial fibrosis.