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Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 1/2011

01-02-2011

RANTES Deficiency Attenuates Autoantibody-Induced Glomerulonephritis

Authors: Chun Xie, Kui Liu, Yuyang Fu, Xiangmei Qin, Geetha Jonnala, Tao Wang, Hong W. Wang, Michael Maldonado, Xin J. Zhou, Chandra Mohan

Published in: Journal of Clinical Immunology | Issue 1/2011

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Abstract

Experimental autoimmune nephritis in mice and spontaneous lupus nephritis are both associated with elevated expression of several chemokines in the kidneys. Nevertheless, the role that different chemokines play in mediating renal inflammation is far from complete. This study focuses on elucidating the functional role of RANTES, a chemokine that has been noted to be hyper-expressed within the kidneys, both in experimental renal disease as well as in spontaneous lupus nephritis. To elucidate if RANTES was essential for immune-mediated glomerulonephritis, DBA/1 mice that are highly sensitive to nephrotoxic serum nephritis were rendered RANTES-deficient and then tested for disease susceptibility. Nephritis-sensitive DBA/1 mice expressed more RANTES within the diseased kidneys. Compared to wild-type DBA/1 mice, RANTES-deficient DBA/1 mice developed significantly less proteinuria, azotemia, and renal inflammation, with reduced crescent formation and tubulo-interstitial nephritis. These findings indicate that RANTES ablation attenuates immune-mediated nephritis and suggest that this chemokine could be a potential therapeutic target in these diseases.
Literature
1.
Schall TJ, Jongstra J, Dyer BJ, Jorgensen J, Clayberger C, Davis MM, et al. A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988;141:1018–25.PubMed
2.
3.
Brown KD, Zurawski SM, Mosmann TR, Zurawski G. A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. J Immunol. 1989;142:679–87.PubMed
4.
Schall TJ, Bacon K, Toy KJ, Goeddel DV. Selective attraction of monocytes and T-lymphocytes of the memory phenotype by cytokine RANTES. Nature. 1990;347:669–71.CrossRefPubMed
5.
Robinson E, Keystone EC, Schall TJ, Gillett N, Fish EN. Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)-1 beta production by synovial T cells. Clin Exp Immunol. 1995;101:398–407.CrossRefPubMed
6.
Rathanaswami P, Hachicha M, Sadick M, Schall TJ, McColl SR. Expression of the cytokine RANTES in human rheumatoid synovial fibroblasts. Differential regulation of RANTES and interleukin-8 genes by inflammatory cytokines. J Biol Chem. 1993;268(8):5834–9.PubMed
7.
Volin MV, Shah MR, Tokuhira M, Haines GK, Woods JM, Koch AE. RANTES expression and contribution to monocyte chemotaxis in arthritis. Clin Immunol Immunopathol. 1998;89:44–53.CrossRefPubMed
8.
Shahrara S, Proudfoot AE, Woods JM, Ruth JH, Amin MA, Park CC, et al. Amelioration of rat adjuvant-induced arthritis by Met-RANTES. Arthritis Rheum. 2005;52:1907–19.CrossRefPubMed
9.
Plater-Zyberk C, Hoogewerf AJ, Proudfoot AE, Power CA, Wells TN. Effect of a CC chemokine receptor antagonist on collagen induced arthritis in DBA/1 mice. Immunol Lett. 1997;57:117–20.CrossRefPubMed
10.
Barnes DA, Tse J, Kaufhold M, Owen M, Hesselgesser J, Strieter R, et al. Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model. J Clin Investig. 1998;101:2910–9.CrossRefPubMed
11.
Okamoto H, Kamatani N. A CCR-5 antagonist inhibits the development of adjuvant arthritis in rats. Rheumatology. 2006;45:230–2.CrossRefPubMed
12.
Snowden N, Hajeer A, Thomson W, Ollier B. RANTES role in rheumatoid arthritis. Lancet. 1994;343:547–8.CrossRefPubMed
13.
Boiardi L, Macchioni P, Meliconi R, Pulsatelli L, Facchini A, Salvarani C. Relationship between serum RANTES levels and radiological progression in rheumatoid arthritis patients treated with methotrexate. Clin Exp Rheumatol. 1999;17:419–25.PubMed
14.
Ellingsen T, Buus A, Kuno Mller B, Stengaard-Pedersen K. In vitro migration of mononuclear cells towards synovial fluid and plasma from rheumatoid arthritis patients correlates to RANTES synovial fluid levels and to clinical pain parameters. Scand J Rheumatol. 2000;29:216–21.CrossRefPubMed
15.
Suzuki N, Nakajima A, Yoshino S, Matsushima K, Yagita H, Okumura K. Selective accumulation of CCR5+ T lymphocytes into inflamed joints of rheumatoid arthritis. Int Immunol. 1999;11:553–9.CrossRefPubMed
16.
Proudfoot AEI, Buser R, Borlat F, Alouani S, Soler D, Offord RE, et al. Amino-terminally modified RANTES analogues demonstrate differential effects on RANTES receptors. J Biol Chem. 1999;274:32478–85.CrossRefPubMed
17.
Anders H-J, Vielhauer V, Kretzler M, Cohen CD, Segerer S, Luckow B, et al. Chemokine and chemokine receptor expression during initiation and resolution of immune complex glomerulonephritis. J Am Soc Nephrol. 2001;12:919–31.PubMed
18.
Schadde E, Kretzler M, Banas B, Luckow B, Assmann K, Schlondorff D. Expression of chemokines and their receptors in nephrotoxic serum nephritis. Nephrol Dial Transplant. 2000;15:1046–53.CrossRefPubMed
19.
Lloyd CM, Minto AW, Dorf ME, Proudfoot A, Wells TNC, Salant DJ, et al. RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 Is involved in crescent formation and interstitial fibrosis. J Exp Med. 1997;185:1371–80.CrossRefPubMed
20.
Krensky AM, Ahn Y-T. Mechanisms of disease: regulation of RANTES (CCL5) in renal disease. Nat Clin Pract Nephrol. 2007;3:164–70.CrossRefPubMed
21.
Cockwell P, et al. In situ analysis of C-C chemokine mRNA in human glomerulonephritis. Kidney Int. 1998;54:827–36.CrossRefPubMed
22.
Furuichi K, et al. Distinct expression of CCR1 and CCR5 in glomerular interstitial lesions of human glomerular disease. Am J Nephrol. 2000;20:291–9.CrossRefPubMed
23.
Xie C, Zhou XJ, Liu X, Mohan C. Enhanced susceptibility to end-organ disease in the lupus-facilitating NZW mouse strain. Arthritis Rheum. 2003;48:1080–92.CrossRefPubMed
24.
Xie C, Sharma R, Wang H, Zhou XJ, Mohan C. Strain distribution pattern of susceptibility to immune-mediated nephritis. J Immunol. 2004;172:5047–55.PubMed
25.
Fu Y, Du Y, Mohan C. The experimental anti-GBM model as a tool for studying spontaneous lupus nephritis. Clin Immunol. 2007;124:109–18.CrossRefPubMed
26.
Tipping PG, Kitching AR. Glomerulonephritis, Th1 and Th2: what's new? Clin Exp Immunol. 2005;142(2):207–15.CrossRefPubMed
27.
Chan RW, Lai FM, Li EK, Tam LS, Chow KM, Li PK, et al. Messenger RNA expression of RANTES in the urinary sediment of patients with lupus nephritis. Nephrology (Carlton). 2006;11(3):219–25.CrossRef
28.
Eriksson C, Eneslatt K, Ivanoff J, Rantapaa-Dahlqvist S, Sundqvist KG. Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus. Lupus. 2003;12(10):766–74.CrossRefPubMed
29.
Kaneko H, Ogasawara H, Naito T, Akimoto H, Lee S, Hishikawa T, et al. Circulating levels of beta-chemokines in systemic lupus erythematosus. J Rheumatol. 1999;26(3):568–73.PubMed
30.
Moore KJ, Wada T, Barbee SD, Kelley VR. Gene transfer of RANTES elicits autoimmune renal injury in MRL-Fas(1pr) mice. Kidney Int. 1998;53(6):1631–41.CrossRefPubMed
31.
Gao P, Zhou X-Y, Yashiro-Ohtani Y, Yang Y-F, Sugimoto N, Ono S, et al. The unique target specificity of a nonpeptide chemokine receptor antagonist: selective blockade of two Th1 chemokine receptors CCR5 and CXCR3. J Leukoc Biol. 2003;73:273–80.CrossRefPubMed
32.
Panzer U, Schneider A, Wilken J, Thompson DA, Kent SB, Stahl RA. The chemokine receptor antagonist AOP-RANTES reduces monocyte infiltration in experimental glomerulonephritis. Kidney Int. 1999;56:2107–15.CrossRefPubMed
33.
Anders HJ, et al. CC chemokine ligand 5/RANTES chemokine antagonists aggravate glomerulonephritis despite reduction of glomerular leukocyte infiltration. J Immunol. 2003;170:5658–66.PubMed
34.
Anders HJ, Vielhauer V, Frink M, Linde Y, Cohen CD, Blattner SM, et al. A chemokine receptor CCR-1 antagonist reduces renal fibrosis after unilateral ureter ligation. J Clin Investig. 2002;109:251–9.PubMed
35.
Anders HJ, Belemezova E, Elis V, Segerer S, Vielhauer V, Frink M, et al. Late onset of treatment with a chemokine receptor CCR1 antagonist prevents progression of lupus nephritis in MRL-FASlpr mice. J Am Soc Nephrol. 2004;15:1504–13.CrossRefPubMed
36.
Eia V, Luckow B, Vielhauer V, Siveke JT, Linde Y, Sergere S, et al. Chemokine receptor CCR1 but not CCR5 mediates leukocyte recruitment and subsequent renal fibrosis after unilateral ureteral obstruction. J Am Soc Nephrol. 2004;15:337–47.CrossRef
37.
Turner J-E, Paust H-J, Steinmetz OM, Peters A, Meyer-Schwesinger C, Heymann F, et al. CCR5 deficiency aggravates crescentic glomerulonephritis in mice. J Immunol. 2008;181:6546–56.PubMed
38.
Ye DQ, et al. Polymorphisms in the promoter region of RANTES in Han Chinese and their relationship with systemic lupus erythematosus. Arch Dermatol Res. 2005;297:108–13.CrossRefPubMed
39.
Mlynarski WM, et al. Risk of diabetic nephropathy in type I diabetes is associated with functional polymorphisms in RANTES receptor gene (CCR5): a sex-specific effect. Diabetes. 2005;54:3331–5.CrossRefPubMed
Metadata
Title
RANTES Deficiency Attenuates Autoantibody-Induced Glomerulonephritis
Authors
Chun Xie
Kui Liu
Yuyang Fu
Xiangmei Qin
Geetha Jonnala
Tao Wang
Hong W. Wang
Michael Maldonado
Xin J. Zhou
Chandra Mohan
Publication date
01-02-2011
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 1/2011
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-010-9470-x

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