| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0602;
Unit of Industrial Toxicology and Occupational Medicine, Université Catholique de Louvain, Brussels, Belgium; and
Department of Pathology, McMaster University, Hamilton, Ontario, Canada
Leukocyte infiltration is characteristic of lung injury and fibrosis, and its role during tissue repair and fibrosis is incompletely understood. We found that overexpression of IL-5 in transgenic mice (IL-5TG) or by adenoviral gene transfer increased bleomycin (blm)-induced lung injury, fibrosis, and eosinophilia. Surprisingly, blm-treated IL-5-deficient (IL-5-/-) mice also developed pronounced pulmonary fibrosis but characterized by marked T lymphocyte infiltration and absence of eosinophilia. In both murine strains however, induction of lung TGF-
expression was evident. Purified lung eosinophils from blm-treated IL-5TG mice stimulated 
-smooth muscle actin and collagen expression in mouse lung fibroblasts, without affecting proliferation. Furthermore instillation of purified eosinophils into murine lungs resulted in extension of blm-induced lung fibrosis, thus confirming a role for eosinophils. However, lung T lymphocytes from blm-treated IL-5-/- mice were able to stimulate fibroblast proliferation but not -smooth muscle actin or collagen expression. Blocking T cell influx by anti-CD3 Abs abrogated lung fibrosis, thus also implicating T lymphocytes as a key participant in fibrosis. Pulmonary fibrosis in IL-5TG mice was preferentially associated with type 2 cytokines (IL-4 and IL-13), whereas fibrotic lesions in IL-5-/- animals were accompanied by proinflammatory cytokine (TNF-, IL-1, and IFN-
) expression. We suggest that eosinophils and T cells contribute distinctly to the development of blm-induced lung fibrosis potentially via their production of different cytokine components, which ultimately induce TGF- expression that is intimately involved with the fibrosis.
This article has been cited by other articles:
|
|
 |
|
  P. L. Simonian, C. L. Roark, F. Wehrmann, A. M. Lanham, W. K. Born, R. L. O'Brien, and A. P. Fontenot IL-17A-Expressing T Cells Are Essential for Bacterial Clearance in a Murine Model of Hypersensitivity Pneumonitis J. Immunol., May 15, 2009; 182(10): 6540 - 6549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Simonian, C. L. Roark, F. Wehrmann, A. K. Lanham, F. Diaz del Valle, W. K. Born, R. L. O'Brien, and A. P. Fontenot Th17-Polarized Immune Response in a Murine Model of Hypersensitivity Pneumonitis and Lung Fibrosis J. Immunol., January 1, 2009; 182(1): 657 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Morschl, J. G. Molina, J. B. Volmer, A. Mohsenin, R. S. Pero, J.-S. Hong, F. Kheradmand, J. J. Lee, and M. R. Blackburn A3 Adenosine Receptor Signaling Influences Pulmonary Inflammation and Fibrosis Am. J. Respir. Cell Mol. Biol., December 1, 2008; 39(6): 697 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zhang, J. Qian, X. Xing, F.-M. Kong, L. Zhao, M. Chen, and T. S. Lawrence Inhibition of the Tumor Necrosis Factor-{alpha} Pathway Is Radioprotective for the Lung Clin. Cancer Res., March 15, 2008; 14(6): 1868 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. G. Luzina, N. W. Todd, A. T. Iacono, and S. P. Atamas Roles of T lymphocytes in pulmonary fibrosis J. Leukoc. Biol., February 1, 2008; 83(2): 237 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Wallach-Dayan, R. Golan-Gerstl, and R. Breuer Evasion of myofibroblasts from immune surveillance: A mechanism for tissue fibrosis PNAS, December 18, 2007; 104(51): 20460 - 20465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Pottier, C. Chupin, V. Defamie, B. Cardinaud, R. Sutherland, G. Rios, F. Gauthier, P. J. Wolters, Y. Berthiaume, P. Barbry, et al. Relationships between Early Inflammatory Response to Bleomycin and Sensitivity to Lung Fibrosis: A Role for Dipeptidyl-Peptidase I and Tissue Inhibitor of Metalloproteinase-3? Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1098 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. van den Brule, J. Heymans, X. Havaux, J.-C. Renauld, D. Lison, F. Huaux, and O. Denis Profibrotic Effect of IL-9 Overexpression in a Model of Airway Remodeling Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 202 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Pochetuhen, I. G. Luzina, V. Lockatell, J. Choi, N. W. Todd, and S. P. Atamas Complex Regulation of Pulmonary Inflammation and Fibrosis by CCL18 Am. J. Pathol., August 1, 2007; 171(2): 428 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Dhillon, D. Pinson, S. Dhillon, O. Tawfik, M. Danley, M. Davis, O. Nemon, M. Mayo, A. Kumar, Y.-J. Tsai, et al. Bleomycin treatment causes enhancement of virus replication in the lungs of SHIV-infected macaques Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1233 - L1240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Studer and N. Kaminski Towards Systems Biology of Human Pulmonary Fibrosis Proceedings of the ATS, January 1, 2007; 4(1): 85 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Misson, F. Brombacher, M. Delos, D. Lison, and F. Huaux Type 2 immune response associated with silicosis is not instrumental in the development of the disease Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L107 - L113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, A. L. Mora, J. LaVoy, K. L. Brigham, and M. Rojas Increased bleomycin-induced lung injury in mice deficient in the transcription factor T-bet Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L658 - L667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Huaux, M. Gharaee-Kermani, T. Liu, V. Morel, B. McGarry, M. Ullenbruch, S. L. Kunkel, J. Wang, Z. Xing, and S. H. Phan Role of Eotaxin-1 (CCL11) and CC Chemokine Receptor 3 (CCR3) in Bleomycin-Induced Lung Injury and Fibrosis Am. J. Pathol., December 1, 2005; 167(6): 1485 - 1496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. B. Jones, R. P. Hart, and P. G. Popovich Molecular Control of Physiological and Pathological T-Cell Recruitment after Mouse Spinal Cord Injury J. Neurosci., July 13, 2005; 25(28): 6576 - 6583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Barbarin, Z. Xing, M. Delos, D. Lison, and F. Huaux Pulmonary overexpression of IL-10 augments lung fibrosis and Th2 responses induced by silica particles Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L841 - L848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Arras, J. Louahed, J.-F. Heilier, M. Delos, F. Brombacher, J.-C. Renauld, D. Lison, and F. Huaux IL-9 Protects against Bleomycin-Induced Lung Injury: Involvement of Prostaglandins Am. J. Pathol., January 1, 2005; 166(1): 107 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Cavarra, F. Carraro, S. Fineschi, A. Naldini, B. Bartalesi, A. Pucci, and G. Lungarella Early response to bleomycin is characterized by different cytokine and cytokine receptor profiles in lungs Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1186 - L1192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Barbarin, M. Arras, P. Misson, M. Delos, B. McGarry, S. H. Phan, D. Lison, and F. Huaux Characterization of the Effect of Interleukin-10 on Silica-Induced Lung Fibrosis in Mice Am. J. Respir. Cell Mol. Biol., July 1, 2004; 31(1): 78 - 85. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
