Localization of platelet-derived growth factor and insulin-like growth factor I in the fibrotic lung.
To better understand the mechanisms responsible for the increase in numbers of fibroblasts and increased collagen synthesis in fibrotic intestitial lung diseases, platelet-derived growth factor (PDGF)-A and PDGF-B, PDGF receptor-alpha and -beta, insulin-like growth factor I (IGF-I), and IGF-I receptor were evaluated immunohistochemically. Additionally, the messenger ribonucleic acids (mRNAs) for PDGF-A and PDGF-B, PDGF receptor-alpha and -beta, and IGF-I were investigated by in situ hybridization in alveolar macrophages and lung tissues from patients with interstitial lung disease. In specimens of bronchoalveolar lavage fluid (BALF), PDGF-A, PDGF-B, and IGF-I were local in alveolar macrophages in patients with idiopathic pulmonary fibrosis (IPF), patients with sarcoidosis (Sar), and normal individuals. Although there were no differences between IPF and Sar in terms of the staining intensity or number of positive cells, the number of such cells was smaller in the normal controls. In lung tissues with early-stage IPF, PDGF and IGF-I proteins were localized exclusively in alveolar macrophages, mononuclear phagocytes, fibroblasts, alveolar Type II cells, vascular endothelial cells, and vascular smooth-muscle cells. In lung tissues with late-stage IPF and those from normal controls, only alveolar macrophages contained PDGF and IGF-I proteins. Interestingly, the cellular localizations of PDGF receptor-alpha and -beta, and of IGF-I receptor were the same as those of the PDGF and IGF-I proteins in early-stage IPF, whereas these cells were not positive for any of these substances in late-stage IPF or normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
S
S
Homma
I
I
Nagaoka
H
H
Abe
K
K
Takahashi
K
K
Seyama
T
T
Nukiwa
S
S
Kira
D000328:Adult; D003095:Collagen Diseases / Q000150:complications; D004730:Endothelium, Vascular / Q000737:chemistry / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008168:Lung / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000737:chemistry; D010586:Phagocytes / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000032:analysis*; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000235:genetics; D012507:Sarcoidosis / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D017479:Receptors, Platelet-Derived Growth Factor