 |
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
|
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
BASIC SCIENCE |
*Nephrological Center, Medical Policlinic, University of Munich, Munich, Germany; Department of Immunology, Berlex Biosciences, Richmond, California; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Department of Pathology, University of Washington Medical Center, Seattle, Washington; ¶Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany.
Correspondence to Dr. Hans-Joachim Anders, Medizinische Poliklinik LMU, Pettenkoferstr. 8a, 80336 München, Germany. Phone: 49-89-5996856; Fax: 49-89-5996860; E-mail: hjanders{at}med.uni-muenchen.de
ABSTRACT. As chemokine receptor CCR1 and CCR5 expression on circulating leukocytes is thought to contribute to leukocyte recruitment during renal fibrosis, the authors examined the effects of unilateral ureteral obstruction (UUO) in mice deficient for CCR1 or CCR5. Analysis of UUO kidneys from CCR1-deficient mice revealed a reduction of interstitial macrophages and lymphocytes (35% and 55%, respectively) compared with wild-type controls. CCR1-deficient mice had reduced CCR5 mRNA levels in UUO kidneys, which correlated with a reduction of CCR5+ T cell infiltrate as determined by flow cytometry. Interstitial fibroblasts, renal TGF-
1 mRNA expression, interstitial volume, and collagen I deposits were all significantly reduced in CCR1-deficient mice. In contrast, renal leukocytes and fibrosis were unaffected in CCR5-deficient mice with UUO. However, if treated with the CCR1 antagonist BX471, CCR5-deficient mice showed a similar reduction of renal leukocytes and fibrosis as CCR1-deficient mice. To determine the underlying mechanism labeled macrophages and T cells isolated from either wild-type, CCR1-deficient, or CCR5-deficient mice were injected into wild-type mice with UUO. Three hours later, renal cell recruitment was reduced for CCR1-deficient cells or cells pretreated with BX471 compared with CCR5-deficient or wild-type cells. Thus, CCR1 but not CCR5 is required for leukocyte recruitment and fibrosis after UUO in mice. Therefore, CCR1 is a promising target for therapeutic intervention in leukocyte-mediated fibrotic tissue injury, e.g. progressive renal fibrosis.
Related Article
J. Am. Soc. Nephrol. 2004 15: A26-A29.
This article has been cited by other articles:
 |
|
 |
|
  K. Furuichi, J.-L. Gao, R. Horuk, T. Wada, S. Kaneko, and P. M. Murphy Chemokine Receptor CCR1 Regulates Inflammatory Cell Infiltration after Renal Ischemia-Reperfusion Injury J. Immunol., December 15, 2008; 181(12): 8670 - 8676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-E. Turner, H.-J. Paust, O. M. Steinmetz, A. Peters, C. Meyer-Schwesinger, F. Heymann, U. Helmchen, S. Fehr, R. Horuk, U. Wenzel, et al. CCR5 Deficiency Aggravates Crescentic Glomerulonephritis in Mice J. Immunol., November 1, 2008; 181(9): 6546 - 6556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mizuguchi, J. Chen, S. V. Seshan, D. P. Poppas, H. H. Szeto, and D. Felsen A novel cell-permeable antioxidant peptide decreases renal tubular apoptosis and damage in unilateral ureteral obstruction Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1545 - F1553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. van Deventer, Q. P. Wu, D. T. Bergstralh, B. K. Davis, B. P. O'Connor, J. P.-Y. Ting, and J. S. Serody C-C Chemokine Receptor 5 on Pulmonary Fibrocytes Facilitates Migration and Promotes Metastasis via Matrix Metalloproteinase 9 Am. J. Pathol., July 1, 2008; 173(1): 253 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kanamaru, S. Pfirsch, M. Aloulou, F. Vrtovsnik, M. Essig, C. Loirat, G. Deschenes, C. Guerin-Marchand, U. Blank, and R. C. Monteiro Inhibitory ITAM Signaling by Fc{alpha}RI-FcR{gamma} Chain Controls Multiple Activating Responses and Prevents Renal Inflammation J. Immunol., February 15, 2008; 180(4): 2669 - 2678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Eitner, E. Bucher, C. van Roeyen, U. Kunter, S. Rong, C. Seikrit, L. Villa, P. Boor, L. Fredriksson, G. Backstrom, et al. PDGF-C Is a Proinflammatory Cytokine that Mediates Renal Interstitial Fibrosis J. Am. Soc. Nephrol., February 1, 2008; 19(2): 281 - 289. [Full Text] [PDF]
|
|
|
|
|
|
N. C. Henderson, A. C. Mackinnon, S. L. Farnworth, T. Kipari, C. Haslett, J. P. Iredale, F.-T. Liu, J. Hughes, and T. Sethi Galectin-3 Expression and Secretion Links Macrophages to the Promotion of Renal Fibrosis Am. J. Pathol., February 1, 2008; 172(2): 288 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Boor, K. Sebekova, T. Ostendorf, and J. Floege Treatment targets in renal fibrosis Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3391 - 3407. [Full Text] [PDF]
|
|
|
|
|
|
V. Mayer, K. L. Hudkins, F. Heller, H. Schmid, M. Kretzler, U. Brandt, H.-J. Anders, H. Regele, P. J. Nelson, C. E. Alpers, et al. Expression of the chemokine receptor CCR1 in human renal allografts Nephrol. Dial. Transplant., June 1, 2007; 22(6): 1720 - 1729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hamrah, S. Yamagami, Y. Liu, Q. Zhang, S. S. Vora, B. Lu, C. J. Gerard, and M. R. Dana Deletion of the Chemokine Receptor CCR1 Prolongs Corneal Allograft Survival Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1228 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L C W Lit, C K Wong, L S Tam, E K M Li, and C W K Lam Raised plasma concentration and ex vivo production of inflammatory chemokines in patients with systemic lupus erythematosus Ann Rheum Dis, February 1, 2006; 65(2): 209 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chen, Y. Wei, A. Alter, G. C. Sharp, and H. Braley-Mullen Chemokine expression during development of fibrosis versus resolution in a murine model of granulomatous experimental autoimmune thyroiditis J. Leukoc. Biol., September 1, 2005; 78(3): 716 - 724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Li, N. Gokden, M. D. Okusa, R. Bhatt, and D. Portilla Anti-inflammatory effect of fibrate protects from cisplatin-induced ARF Am J Physiol Renal Physiol, August 1, 2005; 289(2): F469 - F480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ninichuk, O. Gross, C. Reichel, A. Khandoga, R. D. Pawar, R. Ciubar, S. Segerer, E. Belemezova, E. Radomska, B. Luckow, et al. Delayed Chemokine Receptor 1 Blockade Prolongs Survival in Collagen 4A3-Deficient Mice with Alport Disease J. Am. Soc. Nephrol., April 1, 2005; 16(4): 977 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Anders, V. Vielhauer, and D. Schlondorff Current paradigms about chemokines as therapeutic targets Nephrol. Dial. Transplant., December 1, 2004; 19(12): 2948 - 2951. [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Anders, E. Belemezova, V. Eis, S. Segerer, V. Vielhauer, G. P. de Lema, M. Kretzler, C. D. Cohen, M. Frink, R. Horuk, et al. Late Onset of Treatment with a Chemokine Receptor CCR1 Antagonist Prevents Progression of Lupus Nephritis in MRL-Fas(lpr) Mice J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1504 - 1513. [Abstract] [Full Text] [PDF]
|
|
|
HOME
CURRENT ISSUE
ARCHIVES
JASN Express
ONLINE SUBMISSION
AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP |
Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673
