Enhanced insulin-like growth factor molecules in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is characterized by activated alveolar macrophages (AM), alveolar epithelial cell proliferation and interstitial matrix, and immune complex deposition. Spontaneous release of competence and progression-type growth factors and their associated binding proteins may contribute to the pathologic features of IPF. To study the role of insulin-like growth factor (IGF) molecules in IPF we evaluated spontaneous release of IGF-I and IGFBP-3 in bronchoalveolar lavage cells from control subjects and from patients with IPF. IGF-I levels were similar compared with those in control subjects. In contrast, IGFBP-3 was significantly increased in IPF. In situ hybridization of open lung biopsies showed IGF-I to be abundant in IPF lung tissue in alveolar macrophages, interstitial mesenchymal cells, and epithelial cells. Northern, Western ligand blotting, reverse transcription PCR, and radioimmunoassay suggested that immune complexes stimulate expression of IGFBP-3 in mononuclear phagocytes in a time- and dose-dependent manner bearing strong similarities to stimulation by LPS. These data are compatible with the hypothesis that IGFBP-3 increases the bioactivity of IGF-I derived from a variety of lung tissues contributing to the fibrosis and remodeling seen in IPF.
Aston
C
C
Department of Medicine and Environmental Medicine, NYU Medical Center, NY 10016, USA.
Jagirdar
J
J
Lee
T C
TC
Hur
T
T
Hintz
R L
RL
Rom
W N
WN
D000328:Adult; D000936:Antigen-Antibody Complex / Q000494:pharmacology; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000503:physiopathology*; D011863:Radioimmunoassay
D000936:Antigen-Antibody Complex; D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D008070:Lipopolysaccharides; D007334:Insulin-Like Growth Factor I