2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2005040426v1 16/12/3592    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Lema, G. P. Articles by Luckow, B. Search for Related Content PubMed PubMed Citation Articles by de Lema, G. P. Articles by Luckow, B.

Chemokine Receptor Ccr2 Deficiency Reduces Renal Disease and Prolongs Survival in MRL/lpr Lupus-Prone Mice

Guillermo Pérez de Lema^*, Holger Maier^*, Tobias J. Franz, Maríia Escribese, Silvia Chilla^*, Stephan Segerer^*, Natalia Camarasa, Holger Schmid^*, Bernhard Banas^*, Svetoslav Kalaydjiev, Dirk H. Busch^,, Klaus Pfeffer^||, Francisco Mampaso, Detlef Schlöndorff^* and Bruno Luckow^*

^* Klinikum der Universität München, Medizinische Poliklinik - Innenstadt, Munich, Germany; German Mouse Clinic, Institute of Experimental Genetics, GSF - National Research Center for Environment and Health, Munich/Neuherberg, Germany; Department of Pathology, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain; Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Munich, Germany; and ^|| Institut für Medizinische Mikrobiologie, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, Germany

Address correspondence to: Dr. Bruno Luckow, Klinikum der Universität München, Medizinische Poliklinik - Innenstadt, Arbeitsgruppe Klinische Biochemie, Schillerstrasse 42, D-80336 München, Germany. Phone: +49-89-2180-75842; Fax: +49-89-2180-75860; E-mail:bruno.luckow{at}med.uni-muenchen.de

Received for publication May 2, 2005. Accepted for publication September 22, 2005.

MRL/MpJ-Fas^lpr/J (MRL/lpr) mice represent a well-established mouse model of human systemic lupus erythematosus. MRL/lpr mice homozygous for the spontaneous lymphoproliferation mutation (lpr) are characterized by systemic autoimmunity, massive lymphadenopathy associated with proliferation of aberrant T cells, splenomegaly, hypergammaglobulinemia, arthritis, and fatal immune complex–mediated glomerulonephritis. It was reported previously that steady-state mRNA levels for the chemokine (C-C motif) receptor 2 (Ccr2) continuously increase in kidneys of MRL/lpr mice. For examining the role of Ccr2 for development and progression of immune complex–mediated glomerulonephritis, Ccr2-deficient mice were generated and backcrossed onto the MRL/lpr genetic background. Ccr2-deficient MRL/lpr mice developed less lymphadenopathy, had less proteinuria, had reduced lesion scores, and had less infiltration by T cells and macrophages in the glomerular and tubulointerstitial compartment. Ccr2-deficient MRL/lpr mice survived significantly longer than MRL/lpr wild-type mice despite similar levels of circulating immunoglobulins and comparable immune complex depositions in the glomeruli of both groups. Anti-dsDNA antibody levels, however, were reduced in the absence of Ccr2. The frequency of CD8⁺ T cells in peripheral blood was significantly lower in Ccr2-deficient MRL/lpr mice. Thus Ccr2 deficiency influenced not only monocyte/macrophage and T cell infiltration in the kidney but also the systemic T cell response in MRL/lpr mice. These data suggest an important role for Ccr2 both in the general development of autoimmunity and in the renal involvement of the lupus-like disease. These results identify Ccr2 as an additional possible target for the treatment of lupus nephritis.

This article has been cited by other articles:

				D. R. Engel, J. Maurer, A. P. Tittel, C. Weisheit, T. Cavlar, B. Schumak, A. Limmer, N. van Rooijen, C. Trautwein, F. Tacke, et al. CCR2 Mediates Homeostatic and Inflammatory Release of Gr1high Monocytes from the Bone Marrow, but Is Dispensable for Bladder Infiltration in Bacterial Urinary Tract Infection J. Immunol., October 15, 2008; 181(8): 5579 - 5586. [Abstract] [Full Text] [PDF]

				J. Park, D.-R. Ryu, J. J. Li, D.-S. Jung, S.-J. Kwak, S. H. Lee, T.-H. Yoo, S. H. Han, J. E. Lee, D. K. Kim, et al. MCP-1/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells Am J Physiol Renal Physiol, September 1, 2008; 295(3): F749 - F757. [Abstract] [Full Text] [PDF]

				O. Kulkarni, R. D. Pawar, W. Purschke, D. Eulberg, N. Selve, K. Buchner, V. Ninichuk, S. Segerer, V. Vielhauer, S. Klussmann, et al. Spiegelmer Inhibition of CCL2/MCP-1 Ameliorates Lupus Nephritis in MRL-(Fas)lpr Mice J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2350 - 2358. [Abstract] [Full Text] [PDF]

				M. D. Wareing, A. Lyon, C. Inglis, F. Giannoni, I. Charo, and S. R. Sarawar Chemokine regulation of the inflammatory response to a low-dose influenza infection in CCR2-/- mice J. Leukoc. Biol., March 1, 2007; 81(3): 793 - 801. [Abstract] [Full Text] [PDF]

				A. Y. Hoi, M. J. Hickey, P. Hall, J. Yamana, K. M. O'Sullivan, L. L. Santos, W. G. James, A. R. Kitching, and E. F. Morand Macrophage Migration Inhibitory Factor Deficiency Attenuates Macrophage Recruitment, Glomerulonephritis, and Lethality in MRL/lpr Mice J. Immunol., October 15, 2006; 177(8): 5687 - 5696. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673