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Regular Articles |
From the Departments of Pathology and Laboratory
Medicine*
and Pulmonary
Medicine,
Veterans Affairs Medical Center, Ann
Arbor, Michigan; the Department of Pathology,
University of Michigan Hospitals, Ann Arbor, Michigan; and the
Gladstone Institute of Cardiovascular Disease,§
University of California, San Francisco, California
Monocyte chemotactic protein (MCP)-1 is postulated to play a role
in cellular recruitment during inflammatory reactions. C-C chemokine
receptor 2 (CCR2) is considered the major G-protein coupled receptor
for MCP-1/JE. We reported that mice with knockout of the CCR2 gene
display partially impaired type-1 granuloma formation. The present
study similarly examined the effect of CCR2 deficiency on synchronously
developing type-2 (Th2) cytokine-mediated lung granulomas elicited by
embolization of beads coated with Ags of Schistosoma
mansoni eggs. Systemically, blood monocytes were reduced
by about half throughout the 8-day study period. At the local
level, granuloma size and macrophage content were impaired
during the early growth phase (days 1 to 2). By day 4,
granuloma sizes were similar to controls. In granulomatous
lungs, CCR2 knockout increased mRNA for CCR2 agonists,
MCP-1, MCP-3, and MCP-5, but reduced IL-4 and
IFN
mRNA. The latter was possibly related to decreased CD4+ T cell
recruitment. Regionally, draining lymph nodes showed
panlymphoid hyperplasia with impaired production of IFN,
IL-2, and IL-4, but not IL-5, IL-10, or
IL-13. Analysis of procollagen gene expression indicated transient
impairment of procollagen III transcripts on day 4 of granuloma
formation. These findings indicate that agonists of CCR2 contribute to
multiple facets of type-2 hypersensitivity granulomatous
inflammation.
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N. Sato, S. K. Ahuja, M. Quinones, V. Kostecki, R. L. Reddick, P. C. Melby, W. A. Kuziel, and S. S. Ahuja CC Chemokine Receptor (CCR)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-inducing Dendritic Cells: Absence of CCR2 Shifts the Leishmania major-resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation J. Exp. Med., July 10, 2000; 192(2): 205 - 218. [Abstract] [Full Text] [PDF]
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R. Salcedo, M. L. Ponce, H. A. Young, K. Wasserman, J. M. Ward, H. K. Kleinman, J. J. Oppenheim, and W. J. Murphy Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression Blood, July 1, 2000; 96(1): 34 - 40. [Abstract] [Full Text] [PDF]
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P. G. Andres, P. L. Beck, E. Mizoguchi, A. Mizoguchi, A. K. Bhan, T. Dawson, W. A. Kuziel, N. Maeda, R. P. MacDermott, D. K. Podolsky, et al. Mice with a Selective Deletion of the CC Chemokine Receptors 5 or 2 Are Protected from Dextran Sodium Sulfate-Mediated Colitis: Lack of CC Chemokine Receptor 5 Expression Results in a NK1.1+ Lymphocyte-Associated Th2-Type Immune Response in the Intestine J. Immunol., June 15, 2000; 164(12): 6303 - 6312. [Abstract] [Full Text] [PDF]
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C. M. Hogaboam, C. L. Bone-Larson, M. L. Steinhauser, A. Matsukawa, J. Gosling, L. Boring, I. F. Charo, K. J. Simpson, N. W. Lukacs, and S. L. Kunkel Exaggerated Hepatic Injury Due to Acetaminophen Challenge in Mice Lacking C-C Chemokine Receptor 2 Am. J. Pathol., April 1, 2000; 156(4): 1245 - 1252. [Abstract] [Full Text] [PDF]
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A. Tokuda, M. Itakura, N. Onai, H. Kimura, T. Kuriyama, and K. Matsushima Pivotal Role of CCR1-Positive Leukocytes in Bleomycin- Induced Lung Fibrosis in Mice J. Immunol., March 1, 2000; 164(5): 2745 - 2751. [Abstract] [Full Text] [PDF]
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A. Matsukawa, N. W. Lukacs, T. J. Standiford, S. W. Chensue, and S. L. Kunkel Adenoviral-Mediated Overexpression of Monocyte Chemoattractant Protein-1 Differentially Alters the Development of Th1 and Th2 Type Responses In Vivo J. Immunol., February 15, 2000; 164(4): 1699 - 1704. [Abstract] [Full Text] [PDF]
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T. R. Traynor, W. A. Kuziel, G. B. Toews, and G. B. Huffnagle CCR2 Expression Determines T1 Versus T2 Polarization During Pulmonary Cryptococcus neoformans Infection J. Immunol., February 15, 2000; 164(4): 2021 - 2027. [Abstract] [Full Text] [PDF]
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C. M. Hogaboam, C. L. Bone-Larson, S. Lipinski, N. W. Lukacs, S. W. Chensue, R. M. Strieter, and S. L. Kunkel Differential Monocyte Chemoattractant Protein-1 and Chemokine Receptor 2 Expression by Murine Lung Fibroblasts Derived from Th1- and Th2-Type Pulmonary Granuloma Models J. Immunol., August 15, 1999; 163(4): 2193 - 2201. [Abstract] [Full Text] [PDF]
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