| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 150, 59-66, Copyright © 1997 by American Society for Investigative Pathology
REGULAR ARTICLES |
Z Xing, GM Tremblay, PJ Sime and J Gauldie
Molecular Virology and Immunology Program, McMaster University, Hamilton, Ontario, Canada.
We have previously reported that transfer to rat lung of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene leads to high expression of GM-CSF between days 1 and 4 and granulation tissue formation followed by an irreversible fibrotic response starting from day 12 onward. In the current study, we investigated the underlying mechanisms. We found that GM-CSF overexpression did not enhance production of tumor necrosis factor-alpha in a significant manner at any time after GM-CSF gene transfer. However, the content of transforming growth factor-beta 1 in bronchoalveolar lavage fluid was markedly induced at day 4 and appeared to be maximal around day 7 and remained high at day 12. Macrophages purified from bronchoalveolar lavage fluid 7 days after GM-CSF gene transfer spontaneously released significant quantities of transforming growth factor-beta 1 protein in vitro. After peak transforming growth factor-beta 1 production was the emergence of alpha-smooth muscle actin-rich myofibroblasts. Accumulation of these cells was most prominent at day 12 within the granulation tissues and they were still present in fibrotic areas between days 12 and 24 and diminished markedly afterward. Thus, we provide the first in vivo evidence that tumor necrosis factor-alpha may be dissociated from participation in a fibrotic process in the lung and GM-CSF may play a more direct role in pulmonary fibrogenesis at least in part through its capability to induce transforming growth factor- beta 1 in macrophages and the subsequent emergence of myofibroblast phenotypes. This GM-CSF transgene lung model is useful for a stepwise dissection of both cellular and molecular events involved in pulmonary fibrosis.
This article has been cited by other articles:
 |
|
 |
|
  B. B. Moore and C. M. Hogaboam Murine models of pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L152 - L160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ask, G. E. M. Martin, M. Kolb, and J. Gauldie Targeting genes for treatment in idiopathic pulmonary fibrosis: challenges and opportunities, promises and pitfalls. Proceedings of the ATS, January 1, 2006; 3(4): 389 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. CORDOVA, M. TRIPOLI, B. CORRADINO, P. NAPOLI, and F. MOSCHELLA Dupuytren's Contracture: An Update of Biomolecular Aspects and Therapeutic Perspectives J Hand Surg Eur Vol., December 1, 2005; 30(6): 557 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. Derbigny, M. S. Kerr, and R. M. Johnson Pattern Recognition Molecules Activated by Chlamydia muridarum Infection of Cloned Murine Oviduct Epithelial Cell Lines J. Immunol., November 1, 2005; 175(9): 6065 - 6075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Yoshimoto, S. Togo, T. Kubota, N. Kamimukai, S. Saito, Y. Nagano, I. Endo, H. Sekido, Y. Nagashima, and H. Shimada Role of transforming growth factor-{beta}1 (TGF-{beta}1) in endotoxin-induced hepatic failure after extensive hepatectomy in rats Innate Immunity, February 1, 2005; 11(1): 33 - 39. [Abstract] [PDF]
|
|
|
|
 |
|
 U. Bartram and C. P. Speer The Role of Transforming Growth Factor {beta} in Lung Development and Disease Chest, February 1, 2004; 125(2): 754 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fujita, J. M. Shannon, O. Morikawa, J. Gauldie, N. Hara, and R. J. Mason Overexpression of Tumor Necrosis Factor-{alpha} Diminishes Pulmonary Fibrosis Induced by Bleomycin or Transforming Growth Factor-{beta} Am. J. Respir. Cell Mol. Biol., December 1, 2003; 29(6): 669 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gauldie, T. Galt, P. Bonniaud, C. Robbins, M. Kelly, and D. Warburton Transfer of the Active Form of Transforming Growth Factor-{beta}1 Gene to Newborn Rat Lung Induces Changes Consistent with Bronchopulmonary Dysplasia Am. J. Pathol., December 1, 2003; 163(6): 2575 - 2584. [Abstract] [Full Text]
|
|
|
|
|
|
R. P. Charbeneau, P. J. Christensen, C. J. Chrisman, R. Paine III, G. B. Toews, M. Peters-Golden, and B. B. Moore Impaired synthesis of prostaglandin E2 by lung fibroblasts and alveolar epithelial cells from GM-CSF-/- mice: implications for fibroproliferation Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L1103 - L1111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chen, G. Grotendorst, T. Eichholtz, and N. Khalil GM-CSF increases airway smooth muscle cell connective tissue expression by inducing TGF-beta receptors Am J Physiol Lung Cell Mol Physiol, March 1, 2003; 284(3): L548 - L556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Kunz-Schughart, S. Wenninger, T. Neumeier, P. Seidl, and R. Knuechel Three-dimensional tissue structure affects sensitivity of fibroblasts to TGF-beta 1 Am J Physiol Cell Physiol, January 1, 2003; 284(1): C209 - C219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Burg, V. Krump-Konvalinkova, F. Bittinger, and C. J. Kirkpatrick GM-CSF expression by human lung microvascular endothelial cells: in vitro and in vivo findings Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L460 - L467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Nash, M. T. Deavers, and R. S. Freedman The Expression of Decorin in Human Ovarian Tumors Clin. Cancer Res., June 1, 2002; 8(6): 1754 - 1760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Flaherty, M. M. Monick, A. B. Carter, M. W. Peterson, and G. W. Hunninghake GM-CSF Increases AP-1 DNA Binding and Ref-1 Amounts in Human Alveolar Macrophages Am. J. Respir. Cell Mol. Biol., August 1, 2001; 25(2): 254 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. KOLB, P. J. MARGETTS, T. GALT, P. J. SIME, Z. XING, M. SCHMIDT, and J. GAULDIE Transient Transgene Expression of Decorin in the Lung Reduces the Fibrotic Response to Bleomycin Am. J. Respir. Crit. Care Med., March 1, 2001; 163(3): 770 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Wunderlich, I. C. Moura, and H. A. del Portillo Genetic Immunization of BALB/c mice with a Plasmid Bearing the Gene Coding for a Hybrid Merozoite Surface Protein 1-Hepatitis B Virus Surface Protein Fusion Protects Mice against Lethal Plasmodium chabaudi chabaudi PC1 Infection Infect. Immun., October 1, 2000; 68(10): 5839 - 5845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. B. Moore, M. J. Coffey, P. Christensen, S. Sitterding, R. Ngan, C. A. Wilke, R. McDonald, S. M. Phare, M. Peters-Golden, R. Paine III, et al. GM-CSF Regulates Bleomycin-Induced Pulmonary Fibrosis Via a Prostaglandin-Dependent Mechanism J. Immunol., October 1, 2000; 165(7): 4032 - 4039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Christensen, M. B. Bailie, R. E. Goodman, A. D. O'Brien, G. B. Toews, and R. Paine III Role of diminished epithelial GM-CSF in the pathogenesis of bleomycin-induced pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L487 - L495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-L. Bochaton-Piallat, A. D. Kapetanios, G. Donati, M. Redard, G. Gabbiani, and C. J. Pournaras TGF-{beta}1, TGF-{beta} Receptor II and ED-A Fibronectin Expression in Myofibroblast of Vitreoretinopathy Invest. Ophthalmol. Vis. Sci., July 1, 2000; 41(8): 2336 - 2342. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Vassallo, J. H. Ryu, T. V. Colby, T. Hartman, and A. H. Limper Pulmonary Langerhans'-Cell Histiocytosis N. Engl. J. Med., June 29, 2000; 342(26): 1969 - 1978. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Chegini, X.-M. Tang, and C. Ma Regulation of Transforming Growth Factor-{beta}1 Expression by Granulocyte Macrophage-Colony-Stimulating Factor in Leiomyoma and Myometrial Smooth Muscle Cells J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4138 - 4143. [Abstract] [Full Text]
|
|
|
|
|
|
P. M. Anderson, S. N. Markovic, J. A. Sloan, M. L. Clawson, M. Wylam, C. A. S. Arndt, W. A. Smithson, P. Burch, M. Gornet, and E. Rahman Aerosol Granulocyte Macrophage-Colony Stimulating Factor: A Low Toxicity, Lung-specific Biological Therapy in Patients with Lung Metastases Clin. Cancer Res., September 1, 1999; 5(9): 2316 - 2323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Chegini, H. Rong, B. Bennett, and I. K. Stone Peritoneal Fluid Cytokine and Eicosanoid Levels and Their Relation to the Incidence of Peritoneal Adhesion Reproductive Sciences, May 1, 1999; 6(3): 153 - 157. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Chegini, X.-M. Tang, and Q. Dou The expression, activity and regulation of granulocyte macrophage-colony stimulating factor in human endometrial epithelial and stromal cells Mol. Hum. Reprod., May 1, 1999; 5(5): 459 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P. J. Sime, R. A. Marr, D. Gauldie, Z. Xing, B. R. Hewlett, F. L. Graham, and J. Gauldie Transfer of Tumor Necrosis Factor-{alpha} to Rat Lung Induces Severe Pulmonary Inflammation and Patchy Interstitial Fibrogenesis with Induction of Transforming Growth Factor-ß1 and Myofibroblasts Am. J. Pathol., September 1, 1998; 153(3): 825 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Gabbiani Evolution and clinical implications of the myofibroblast concept Cardiovasc Res, June 1, 1998; 38(3): 545 - 548. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
