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

Abstract

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.