C Aston, J Jagirdar, TC Lee, T Hur, RL Hintz and WN Rom
Department of Medicine and Environmental Medicine, NYU Medical Center, NY 10016, USA.

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.

This article has been cited by other articles:

				R. M. Strieter and B. Mehrad New Mechanisms of Pulmonary Fibrosis Chest, November 1, 2009; 136(5): 1364 - 1370. [Abstract] [Full Text] [PDF]

				R. M. Strieter, E. C. Keeley, M. A. Hughes, M. D. Burdick, and B. Mehrad The role of circulating mesenchymal progenitor cells (fibrocytes) in the pathogenesis of pulmonary fibrosis J. Leukoc. Biol., November 1, 2009; 86(5): 1111 - 1118. [Abstract] [Full Text] [PDF]

				R. S. Douglas, A. G. Gianoukakis, S. Kamat, and T. J. Smith Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves' Disease May Carry Functional Consequences for Disease Pathogenesis J. Immunol., March 1, 2007; 178(5): 3281 - 3287. [Abstract] [Full Text] [PDF]

				L. M. Schnapp, S. Donohoe, J. Chen, D. A. Sunde, P. M. Kelly, J. Ruzinski, T. Martin, and D. R. Goodlett Mining the Acute Respiratory Distress Syndrome Proteome: Identification of the Insulin-Like Growth Factor (IGF)/IGF-Binding Protein-3 Pathway in Acute Lung Injury Am. J. Pathol., July 1, 2006; 169(1): 86 - 95. [Abstract] [Full Text] [PDF]

				M. Selman, A. Pardo, L. Barrera, A. Estrada, S. R. Watson, K. Wilson, N. Aziz, N. Kaminski, and A. Zlotnik Gene Expression Profiles Distinguish Idiopathic Pulmonary Fibrosis from Hypersensitivity Pneumonitis Am. J. Respir. Crit. Care Med., January 15, 2006; 173(2): 188 - 198. [Abstract] [Full Text] [PDF]

				C. A. Feghali-Bostwick IGF-I: mediator of fibrosis or carcinogenesis? Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L803 - L804. [Full Text] [PDF]

				J. M. Pilewski, L. Liu, A. C. Henry, A. V. Knauer, and C. A. Feghali-Bostwick Insulin-Like Growth Factor Binding Proteins 3 and 5 Are Overexpressed in Idiopathic Pulmonary Fibrosis and Contribute to Extracellular Matrix Deposition Am. J. Pathol., February 1, 2005; 166(2): 399 - 407. [Abstract] [Full Text] [PDF]

				P. M. Krein, P. J. B. Sabatini, W. Tinmouth, F. H. Y. Green, and B. W. Winston Localization of Insulin-like Growth Factor-I in Lung Tissues of Patients with Fibroproliferative Acute Respiratory Distress Syndrome Am. J. Respir. Crit. Care Med., January 1, 2003; 167(1): 83 - 90. [Abstract] [Full Text] [PDF]

				M. K. Winkler and J. L. Fowlkes Metalloproteinase and growth factor interactions: do they play a role in pulmonary fibrosis? Am J Physiol Lung Cell Mol Physiol, July 1, 2002; 283(1): L1 - L11. [Abstract] [Full Text] [PDF]

				W. A. Price, B. M. Moats-Staats, and A. D. Stiles Pro- and Anti-inflammatory Cytokines Regulate Insulin-like Growth Factor Binding Protein Production by Fetal Rat Lung Fibroblasts Am. J. Respir. Cell Mol. Biol., March 1, 2002; 26(3): 283 - 289. [Abstract] [Full Text] [PDF]

				C. A. BLOOR, R. A. KNIGHT, R. K. KEDIA, M. A. SPITERI, and J. T. ALLEN Differential mRNA Expression of Insulin-like Growth Factor-1 Splice Variants in Patients With Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis Am. J. Respir. Crit. Care Med., July 15, 2001; 164(2): 265 - 272. [Abstract] [Full Text] [PDF]

				L. V. de Lara, C. Becerril, M. Montano, C. Ramos, V. Maldonado, J. Melendez, D. S. Phelps, A. Pardo, and M. Selman Surfactant components modulate fibroblast apoptosis and type I collagen and collagenase-1 expression Am J Physiol Lung Cell Mol Physiol, November 1, 2000; 279(5): L950 - L957. [Abstract] [Full Text] [PDF]

				J.-M. CHARPIN, M. STERN, D. GRENET, and D. ISRAËL-BIET Insulinlike Growth Factor-1 in Lung Transplants with Obliterative Bronchiolitis Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 1991 - 1998. [Abstract] [Full Text]

				M. Fujiki, T. Shinbori, M. Suga, H. Miyakawa, and M. Ando Role of T Cells in Bronchoalveolar Space in the Development of Interstitial Pneumonia Induced by Superantigen in Autoimmune-Prone Mice Am. J. Respir. Cell Mol. Biol., December 1, 1999; 21(6): 675 - 683. [Abstract] [Full Text]

				J. T. Allen, R. A. Knight, C. A. Bloor, and M. A. Spiteri Enhanced Insulin-Like Growth Factor Binding Protein-Related Protein 2 (Connective Tissue Growth Factor) Expression in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis Am. J. Respir. Cell Mol. Biol., December 1, 1999; 21(6): 693 - 700. [Abstract] [Full Text]

				S.-T. UH, Y. INOUE, T. E. KING Jr., E. D. CHAN, L. S. NEWMAN, and D. W. H. RICHES Morphometric Analysis of Insulin-like Growth Factor-I Localization in Lung Tissues of Patients with Idiopathic Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., November 1, 1998; 158(5): 1626 - 1635. [Abstract] [Full Text] [PDF]

				J. T. Allen, C. A. Bloor, R. A. Knight, and M. A. Spiteri Expression of Insulin-like Growth Factor Binding Proteins in Bronchoalveolar Lavage Fluid of Patients with Pulmonary Sarcoidosis Am. J. Respir. Cell Mol. Biol., August 1, 1998; 19(2): 250 - 258. [Abstract] [Full Text]

				P. A. WARD and G. W. HUNNINGHAKE Lung Inflammation and Fibrosis Am. J. Respir. Crit. Care Med., April 1, 1998; 157(4): S123 - S129. [Full Text] [PDF]