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í Plach
*
Medical Policlinic, University of Munich, Munich, Germany;
Institute for Animal Physiology, University of Munich, Munich, Germany;
Serono Pharmaceutical Research Institute, Geneva, Switzerland; and
Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic
The chemokine receptors CCR2 and CCR5 play important roles in the
recruitment of monocytes/macrophages and T cells. To better understand
the role of both receptors in murine models of inflammatory diseases
and to recognize potential problems when correlating these data to
humans, we have generated mAbs against murine CCR2 and CCR5. In mice
CCR2 is homogeneously expressed on monocytes and on 2–15% of T cells,
closely resembling the expression pattern in humans. In contrast to
humans, murine NK cells are highly CCR5 positive. In addition, CCR5 is
expressed on 3–10% of CD4 and 10–40% of CD8-positive T cells and is
weakly detectable on monocytes. Using a model of immune complex
nephritis, we examined the effects of inflammation on chemokine
receptor expression and found a 10-fold enrichment of CCR5+
and CCR2+ T cells in the inflamed kidneys. The activity of
various chemokines and the antagonistic properties of the mAbs were
measured by ligand-induced internalization of CCR2 and CCR5 on primary
leukocytes. The Ab MC-21 (anti-CCR2) reduced the activity of murine
monocyte chemotactic protein 1 by 95%, whereas the Ab MC-68
(anti-CCR5) blocked over 99% of the macrophage-inflammatory
protein 1
and RANTES activity. MC-21 and MC-68 efficiently blocked
the ligand binding to CCR2 and CCR5 with an IC50 of 0.09
and 0.6–1.0 µg/ml, respectively. In good correlation to these in
vitro data, MC-21 almost completely prevented the influx of monocytes
in thioglycollate-induced peritonitis. Therefore, both Abs appear as
useful reagents to further study the role of CCR2 and CCR5 in murine
disease models.
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H. Xu, A. Manivannan, R. Dawson, I. J. Crane, M. Mack, P. Sharp, and J. Liversidge Differentiation to the CCR2+ Inflammatory Phenotype In Vivo Is a Constitutive, Time-Limited Property of Blood Monocytes and Is Independent of Local Inflammatory Mediators J. Immunol., November 15, 2005; 175(10): 6915 - 6923. [Abstract] [Full Text] [PDF]
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J. S. Duffield, P. G. Tipping, T. Kipari, J.-F. Cailhier, S. Clay, R. Lang, J. V. Bonventre, and J. Hughes Conditional Ablation of Macrophages Halts Progression of Crescentic Glomerulonephritis Am. J. Pathol., November 1, 2005; 167(5): 1207 - 1219. [Abstract] [Full Text] [PDF]
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T. H. Terwey, T. D. Kim, A. A. Kochman, V. M. Hubbard, S. Lu, J. L. Zakrzewski, T. Ramirez-Montagut, J. M. Eng, S. J. Muriglan, G. Heller, et al. CCR2 is required for CD8-induced graft-versus-host disease Blood, November 1, 2005; 106(9): 3322 - 3330. [Abstract] [Full Text] [PDF]
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C. A. Wysocki, A. Panoskaltsis-Mortari, B. R. Blazar, and J. S. Serody Leukocyte migration and graft-versus-host disease Blood, June 1, 2005; 105(11): 4191 - 4199. [Abstract] [Full Text] [PDF]
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K. L. Hokeness, W. A. Kuziel, C. A. Biron, and T. P. Salazar-Mather Monocyte Chemoattractant Protein-1 and CCR2 Interactions Are Required for IFN-{alpha}/{beta}-Induced Inflammatory Responses and Antiviral Defense in Liver J. Immunol., February 1, 2005; 174(3): 1549 - 1556. [Abstract] [Full Text] [PDF]
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M. Mack, M. A. Schneider, C. Moll, J. Cihak, H. Bruhl, J. W. Ellwart, M. P. Hogarth, M. Stangassinger, and D. Schlondorff Identification of Antigen-Capturing Cells as Basophils J. Immunol., January 15, 2005; 174(2): 735 - 741. [Abstract] [Full Text] [PDF]
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B.-C. Chiu, C. M. Freeman, V. R. Stolberg, J. S. Hu, K. Zeibecoglou, B. Lu, C. Gerard, I. F. Charo, S. A. Lira, and S. W. Chensue Impaired Lung Dendritic Cell Activation in CCR2 Knockout Mice Am. J. Pathol., October 1, 2004; 165(4): 1199 - 1209. [Abstract] [Full Text] [PDF]
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H. M. Scott Algood and J. L. Flynn CCR5-Deficient Mice Control Mycobacterium tuberculosis Infection despite Increased Pulmonary Lymphocytic Infiltration J. Immunol., September 1, 2004; 173(5): 3287 - 3296. [Abstract] [Full Text] [PDF]
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W. Peters, J. G. Cyster, M. Mack, D. Schlondorff, A. J. Wolf, J. D. Ernst, and I. F. Charo CCR2-Dependent Trafficking of F4/80dim Macrophages and CD11cdim/intermediate Dendritic Cells Is Crucial for T Cell Recruitment to Lungs Infected with Mycobacterium tuberculosis J. Immunol., June 15, 2004; 172(12): 7647 - 7653. [Abstract] [Full Text] [PDF]
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G. C. Hildebrandt, U. A. Duffner, K. M. Olkiewicz, L. A. Corrion, N. E. Willmarth, D. L. Williams, S. G. Clouthier, C. M. Hogaboam, P. R. Reddy, B. B. Moore, et al. A critical role for CCR2/MCP-1 interactions in the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation Blood, March 15, 2004; 103(6): 2417 - 2426. [Abstract] [Full Text] [PDF]
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V. Eis, B. Luckow, V. Vielhauer, J. T. Siveke, Y. Linde, S. Segerer, G. P. de Lema, C. D. Cohen, M. Kretzler, M. Mack, et al. Chemokine Receptor CCR1 But Not CCR5 Mediates Leukocyte Recruitment and Subsequent Renal Fibrosis after Unilateral Ureteral Obstruction J. Am. Soc. Nephrol., February 1, 2004; 15(2): 337 - 347. [Abstract] [Full Text] [PDF]
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H. Bruhl, J. Cihak, M. A. Schneider, J. Plachy, T. Rupp, I. Wenzel, M. Shakarami, S. Milz, J. W. Ellwart, M. Stangassinger, et al. Dual Role of CCR2 during Initiation and Progression of Collagen-Induced Arthritis: Evidence for Regulatory Activity of CCR2+ T Cells J. Immunol., January 15, 2004; 172(2): 890 - 898. [Abstract] [Full Text] [PDF]
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C. Penido, A. Vieira-de-Abreu, M. T. Bozza, H. C. Castro-Faria-Neto, and P. T. Bozza Role of Monocyte Chemotactic Protein-1/CC Chemokine Ligand 2 on {gamma}{delta} T Lymphocyte Trafficking during Inflammation Induced by Lipopolysaccharide or Mycobacterium bovis Bacille Calmette-Guerin J. Immunol., December 15, 2003; 171(12): 6788 - 6794. [Abstract] [Full Text] [PDF]
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I. Lee, L. Wang, A. D. Wells, Q. Ye, R. Han, M. E. Dorf, W. A. Kuziel, B. J. Rollins, L. Chen, and W. W. Hancock Blocking the Monocyte Chemoattractant Protein-1/CCR2 Chemokine Pathway Induces Permanent Survival of Islet Allografts through a Programmed Death-1 Ligand-1-Dependent Mechanism J. Immunol., December 15, 2003; 171(12): 6929 - 6935. [Abstract] [Full Text] [PDF]
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Y. Chvatchko, A. E. I. Proudfoot, R. Buser, P. Juillard, S. Alouani, M. Kosco-Vilbois, A. J. Coyle, R. J. Nibbs, G. Graham, R. E. Offord, et al. Inhibition of Airway Inflammation by Amino-Terminally Modified RANTES/CC Chemokine Ligand 5 Analogues Is Not Mediated through CCR3 J. Immunol., November 15, 2003; 171(10): 5498 - 5506. [Abstract] [Full Text] [PDF]
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M. Crittenden, M. Gough, K. Harrington, K. Olivier, J. Thompson, and R. G. Vile Expression of Inflammatory Chemokines Combined with Local Tumor Destruction Enhances Tumor Regression and Long-term Immunity Cancer Res., September 1, 2003; 63(17): 5505 - 5512. [Abstract] [Full Text] [PDF]
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K.-H. Sonoda, Y. Sasa, H. Qiao, C. Tsutsumi, T. Hisatomi, S. Komiyama, T. Kubota, T. Sakamoto, Y.-I. Kawano, and T. Ishibashi Immunoregulatory Role of Ocular Macrophages: The Macrophages Produce RANTES to Suppress Experimental Autoimmune Uveitis J. Immunol., September 1, 2003; 171(5): 2652 - 2659. [Abstract] [Full Text] [PDF]
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C. Tsutsumi, K.-H. Sonoda, K. Egashira, H. Qiao, T. Hisatomi, S. Nakao, M. Ishibashi, I. F. Charo, T. Sakamoto, T. Murata, et al. The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization J. Leukoc. Biol., July 1, 2003; 74(1): 25 - 32. [Abstract] [Full Text] [PDF]
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U. A. Maus, K. Waelsch, W. A. Kuziel, T. Delbeck, M. Mack, T. S. Blackwell, J. W. Christman, D. Schlondorff, W. Seeger, and J. Lohmeyer Monocytes Are Potent Facilitators of Alveolar Neutrophil Emigration During Lung Inflammation: Role of the CCL2-CCR2 Axis J. Immunol., March 15, 2003; 170(6): 3273 - 3278. [Abstract] [Full Text] [PDF]
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J. Onuffer, M. A. McCarrick, L. Dunning, M. Liang, M. Rosser, G.-P. Wei, H. Ng, and R. Horuk Structure Function Differences in Nonpeptide CCR1 Antagonists for Human and Mouse CCR1 J. Immunol., February 15, 2003; 170(4): 1910 - 1916. [Abstract] [Full Text] [PDF]
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H.-J. Anders, B. Banas, Y. Linde, L. Weller, C. D. Cohen, M. Kretzler, S. Martin, V. Vielhauer, D. Schlondorff, and H.-J. Grone Bacterial CpG-DNA Aggravates Immune Complex Glomerulonephritis: Role of TLR9-Mediated Expression of Chemokines and Chemokine Receptors J. Am. Soc. Nephrol., February 1, 2003; 14(2): 317 - 326. [Abstract] [Full Text] [PDF]
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 G. Wolf, T. Jocks, G. Zahner, U. Panzer, and R. A. K. Stahl Existence of a regulatory loop between MCP-1 and TGF-beta in glomerular immune injury Am J Physiol Renal Physiol, November 1, 2002; 283(5): F1075 - F1084. [Abstract] [Full Text] [PDF]
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 L. Zhang, M. P. Soares, Y. Guan, S. Matheravidathu, R. Wnek, K. E. Johnson, A. Meisher, S. A. Iliff, J. S. Mudgett, M. S. Springer, et al. Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies J. Biol. Chem., September 6, 2002; 277(37): 33799 - 33810. [Abstract] [Full Text] [PDF]
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U. Maus, K. von Grote, W. A. Kuziel, M. Mack, E. J. Miller, J. Cihak, M. Stangassinger, R. Maus, D. Schlondorff, W. Seeger, et al. The Role of CC Chemokine Receptor 2 in Alveolar Monocyte and Neutrophil Immigration in Intact Mice Am. J. Respir. Crit. Care Med., August 1, 2002; 166(3): 268 - 273. [Abstract] [Full Text] [PDF]
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M. Rodriguez-Sosa, A. R. Satoskar, R. Calderon, L. Gomez-Garcia, R. Saavedra, R. Bojalil, and L. I. Terrazas Chronic Helminth Infection Induces Alternatively Activated Macrophages Expressing High Levels of CCR5 with Low Interleukin-12 Production and Th2-Biasing Ability Infect. Immun., July 1, 2002; 70(7): 3656 - 3664. [Abstract] [Full Text] [PDF]
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H. Tomiyama, T. Matsuda, and M. Takiguchi Differentiation of Human CD8+ T Cells from a Memory to Memory/Effector Phenotype J. Immunol., June 1, 2002; 168(11): 5538 - 5550. [Abstract] [Full Text] [PDF]
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 W. I. de Boer Cytokines and Therapy in COPD* : A Promising Combination? Chest, May 1, 2002; 121 (2009): 209S - 218S. [Abstract] [Full Text] [PDF]
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V. VIELHAUER, H.-J. ANDERS, M. MACK, J. CIHAK, F. STRUTZ, M. STANGASSINGER, B. LUCKOW, H.-J. GRÖNE, and D. SCHLÖNDORFF Obstructive Nephropathy in the Mouse: Progressive Fibrosis Correlates with Tubulointerstitial Chemokine Expression and Accumulation of CC Chemokine Receptor 2- and 5-Positive Leukocytes J. Am. Soc. Nephrol., June 1, 2001; 12(6): 1173 - 1187. [Abstract] [Full Text]
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U. A. Maus, M. A. Koay, T. Delbeck, M. Mack, M. Ermert, L. Ermert, T. S. Blackwell, J. W. Christman, D. Schlondorff, W. Seeger, et al. Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1245 - L1252. [Abstract] [Full Text] [PDF]
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