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Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109 and * University of Texas, Austin, TX 78712
Pulmonary fibrosis can be modeled in animals by intratracheal
instillation of FITC, which results in acute lung injury, inflammation,
and extracellular matrix deposition. We have previously shown that
despite chronic inflammation, this model of pulmonary fibrosis is
lymphocyte independent. The CC chemokine monocyte-chemoattractant
protein-1 is induced following FITC deposition. Therefore, we have
investigated the contribution of the main monocyte-chemoattractant
protein-1 chemokine receptor, CCR2, to the fibrotic disease process. We
demonstrate that CCR2-/- mice are protected from fibrosis
in both the FITC and bleomycin pulmonary fibrosis models. The
protection is specific for the absence of CCR2, as
CCR5-/- mice are not protected. The protection is not
explained by differences in acute lung injury, or the magnitude or
composition of inflammatory cells. FITC-treated CCR2-/-
mice display differential patterns of cellular activation as evidenced
by the altered production of cytokines and growth factors following
FITC inoculation compared with wild-type controls.
CCR2-/- mice have increased levels of GM-CSF and reduced
levels of TNF-
compared with FITC-treated CCR2+/+ mice.
Thus, CCR2 signaling promotes a profibrotic cytokine cascade following
FITC administration.
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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]
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M. Dona, I. Dell'Aica, F. Calabrese, R. Benelli, M. Morini, A. Albini, and S. Garbisa Neutrophil Restraint by Green Tea: Inhibition of Inflammation, Associated Angiogenesis, and Pulmonary Fibrosis J. Immunol., April 15, 2003; 170(8): 4335 - 4341. [Abstract] [Full Text] [PDF]
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E. I. Majeski, R. A. Harley, S. C. Bellum, S. D. London, and L. London Differential Role for T Cells in the Development of Fibrotic Lesions Associated with Reovirus 1/L-Induced Bronchiolitis Obliterans Organizing Pneumonia versus Acute Respiratory Distress Syndrome Am. J. Respir. Cell Mol. Biol., February 1, 2003; 28(2): 208 - 217. [Abstract] [Full Text] [PDF]
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B. B. Moore, M. Peters-Golden, P. J. Christensen, V. Lama, W. A. Kuziel, R. Paine III, and G. B. Toews Alveolar epithelial cell inhibition of fibroblast proliferation is regulated by MCP-1/CCR2 and mediated by PGE2 Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L342 - L349. [Abstract] [Full Text] [PDF]
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K. Chen, Y. Wei, G. C. Sharp, and H. Braley-Mullen Inhibition of TGF{beta}1 by Anti-TGF{beta}1 Antibody or Lisinopril Reduces Thyroid Fibrosis in Granulomatous Experimental Autoimmune Thyroiditis J. Immunol., December 1, 2002; 169(11): 6530 - 6538. [Abstract] [Full Text] [PDF]
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J. A. Belperio, M. Dy, M. D. Burdick, Y. Y. Xue, K. Li, J. A. Elias, and M. P. Keane Interaction of IL-13 and C10 in the Pathogenesis of Bleomycin-Induced Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., October 1, 2002; 27(4): 419 - 427. [Abstract] [Full Text] [PDF]
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