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.
Chen
F
F
Department of Immunology, Beijing Medical University, China.
Deng
H Y
HY
Ding
G F
GF
Houng
D W
DW
Deng
Y L
YL
Long
Z Z
ZZ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D007375:Interleukin-1 / Q000032:analysis; D008168:Lung / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide; D012829:Silicosis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D012822:Silicon Dioxide