C. Aston et al., ENHANCED INSULIN-LIKE GROWTH-FACTOR MOLECULES IN IDIOPATHIC PULMONARYFIBROSIS, American journal of respiratory and critical care medicine, 151(5), 1995, pp. 1597-1603
Citations number
35
Categorie Soggetti
Emergency Medicine & Critical Care","Respiratory System
Idiopathic pulmonary fibrosis (IPF) is characterized by activated alve
olar macrophages (AM), alveolar epithelial cell proliferation and inte
rstitial matrix, and immune complex deposition. Spontaneous release of
competence and progression-type growth factors and their associated b
inding proteins may contribute to the pathologic features of IPF. To s
tudy the role of insulinlike growth factor (IGF) molecules in IPF we e
valuated spontaneous release of IGF-I and IGFBP-3 in bronchoalveolar l
avage cells from control subjects and from patients with IPF. IGF-I le
vels 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 c
ells. Northern, Western ligand blotting, reverse transcription PCR, an
d radioimmunoassay suggested that immune complexes stimulate expressio
n of IGFBP-3 in mononuclear phagocytes in a time- and dose-dependent m
anner bearing strong similarities to stimulation by LPS. These data ar
e compatible with the hypothesis that IGFBP-3 increases the bioactivit
y of IGF-I derived from a variety of lung tissues contributing to the
fibrosis and remodeling seen in IPF.