EXCESSIVE PRODUCTION OF INSULIN-LIKE GROWTH-FACTOR-I BY SILICOTIC RATALVEOLAR MACROPHAGES

The supernatant of silicotic rat alveolar macrophages can stimulate fi broblast growth. The present study demonstrates that this activity is mainly attributed to insulin-like growth factor-I. Partial purificatio n of the supernatant of alveolar macrophages, which were from silica-e xposed 5 to 6-week-old rats, revealed a protein peak (peak 5) eluted f rom a molecular-sieve HPLC column, corresponding to a MW of 6-9 kDa. A ctivity assay and radioimmunoassay indicated that this peak is more po tent with regard to stimulation of fibroblast growth and has higher in sulin-like growth factor-I immuno-reactivity, but there was no detecta ble 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 ipl vivo, but no alteration in insulin-like growth factor-I level can be found i n sera. These findings suggest that excessive production ofinsulin-lik e growth factor-I by alveolar macrophages locally may play a pivotal r ole in silica-induced pulmonary interstitial fibrosis.