B Cao1, Z Guo, Y Zhu, W Xu. 1. Department of Respiratory Disease, Peking Union Medical College Hospital, Beijing 100730, China. caobin1999@yahoo.com
Abstract
OBJECTIVE: To identify the role of cytokines involved in the development of lung fibrosis in patients with idiopathic-pulmonary fibrosis (IPF). METHODS: Proteins and gene expression of platelet-derived growth factor (PDGF)-A and -B, insulin-like growth factor 1 (IGF-1), and transforming growth factor beta (TGF-beta) were measured in alveolar macrophages and open lung biopsies from patients with IPF using immunohistochemistry (IHC) and in situ hybridization (ISH). RESULTS: In specimens of bronchoalveolar lavage fluid (BALF), PDGF-A, PDGF-B, IGF-1, TGF-beta were localized in alveolar macrophages. Evaluation of open lung biopsies from patients with IPF showed that IGF-1 was prominently present in pulmonary vessel walls in fibrotic lesions. PDGF and TGF-beta proteins were localized to hyperplastic bronchio-alveolar epithelial cells, alveolar macrophages, fibroblasts, vascular smooth muscle and endothelial cells. Our in situ hybridization results were consistent with that of immunohistochemistry except that PDGF-A and TGF-beta mRNA transcripts were not detected in bronchoalveolar epithelial cells. CONCLUSION: These observations suggest that (1) alveolar macrophages play key roles not only in inflammation but also in the fibrotic process by releasing PDGF, IGF-1 and TGF-beta; (2) IGF-1 could be responsible for angiogenesis in IPF; (3) PDGF, TGF-beta are associated with fibroplasia and the deposition of extracellular matrix, as well as vessel remodeling and epithelial cell repopularization.
OBJECTIVE: To identify the role of cytokines involved in the development of lung fibrosis in patients with idiopathic-pulmonary fibrosis (IPF). METHODS: Proteins and gene expression of platelet-derived growth factor (PDGF)-A and -B, insulin-like growth factor 1 (IGF-1), and transforming growth factor beta (TGF-beta) were measured in alveolar macrophages and open lung biopsies from patients with IPF using immunohistochemistry (IHC) and in situ hybridization (ISH). RESULTS: In specimens of bronchoalveolar lavage fluid (BALF), PDGF-A, PDGF-B, IGF-1, TGF-beta were localized in alveolar macrophages. Evaluation of open lung biopsies from patients with IPF showed that IGF-1 was prominently present in pulmonary vessel walls in fibrotic lesions. PDGF and TGF-beta proteins were localized to hyperplastic bronchio-alveolar epithelial cells, alveolar macrophages, fibroblasts, vascular smooth muscle and endothelial cells. Our in situ hybridization results were consistent with that of immunohistochemistry except that PDGF-A and TGF-beta mRNA transcripts were not detected in bronchoalveolar epithelial cells. CONCLUSION: These observations suggest that (1) alveolar macrophages play key roles not only in inflammation but also in the fibrotic process by releasing PDGF, IGF-1 and TGF-beta; (2) IGF-1 could be responsible for angiogenesis in IPF; (3) PDGF, TGF-beta are associated with fibroplasia and the deposition of extracellular matrix, as well as vessel remodeling and epithelial cell repopularization.
Authors: Martina Ulrich; Dieter Worlitzsch; Simona Viglio; Nanna Siegmann; Paolo Iadarola; Janis K Shute; Marianne Geiser; Gerald B Pier; Godehard Friedel; Mark L Barr; Antje Schuster; Keith C Meyer; Felix Ratjen; Thomas Bjarnsholt; Erich Gulbins; Gerd Döring Journal: J Cyst Fibros Date: 2010-03-29 Impact factor: 5.482