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World Journal of Urology

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Open Access 01-08-2010 | Original Article

Viral macrophage inflammatory protein-II improves acute rejection in allogeneic rat kidney transplants

Authors: Jens Bedke, Tomislav Stojanovic, Eva Kiss, Carl-Ludwig Behnes, Amanda E. Proudfoot, Hermann-Josef Gröne

Published in: World Journal of Urology | Issue 4/2010

Abstract

Purpose

During rejection, leukocytes are recruited from the peripheral circulation into the graft leading to the damage of endothelial cells, capillary perfusion failure and graft loss. Chemokines play a pivotal role in the recruitment of leukocytes to the endothelium. Viral macrophage inflammatory protein-II (vMIP-II), a human herpes virus-8 DNA-encoded protein, is a broad-spectrum chemokine antagonist. The aim of the study was to prove the beneficial activity of vMIP-II treatment on acute rat kidney allograft damage.

Methods

Heterotopic rat kidney transplantation was performed in the Fischer 344 to Lewis transplantation model and animals were treated with vMIP-II (2 × 15 µg or 100 µg/day) for 7 days. Rejection-induced damage was analyzed by histology, and microcirculatory changes within the graft were analyzed by in vivo microscopy.

Results

Viral macrophage inflammatory protein-II significantly improved acute glomerular damage and tubulointerstitial inflammation and lowered the extent of vascular and tubulointerstitial damage of the treated allografts. Functional microcirculation of peritubular capillaries was significantly improved in vivo, and the firm adherence of leukocytes was significantly reduced by vMIP-II treatment.

Conclusions

The administration of the broad-spectrum antagonist vMIP-II improved acute renal allograft damage, mainly by a reduction in leukocyte recruitment with a subsequently improved renal cortical microcirculation in vivo.

Grone HJ et al (1999) Met-RANTES reduces vascular and tubular damage during acute renal transplant rejection: blocking monocyte arrest and recruitment. FASEB J 13:1371–1383PubMed

Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314CrossRefPubMed

Nelson PJ, Krensky AM (2001) Chemokines and allograft rejection: narrowing the list of suspects. Transplantation 72:1195–1197CrossRefPubMed

Bedke J et al (2007) Beneficial effects of CCR1 blockade on the progression of chronic renal allograft damage. Am J Transplant 7:527–537CrossRefPubMed

Hancock WW et al (2003) Chemokines and their receptors as markers of allograft rejection and targets for immunosuppression. Curr Opin Immunol 15:479–486CrossRefPubMed

Chen S et al (1998) In vivo inhibition of CC and CX3C chemokine-induced leukocyte infiltration and attenuation of glomerulonephritis in Wistar–Kyoto (WKY) rats by vMIP-II. J Exp Med 188:193–198CrossRefPubMed

Pillai RG et al (2008) Expression of the chemokine antagonist vMIP II using a non-viral vector can prolong corneal allograft survival. Transplantation 85:1640–1647CrossRefPubMed

DeBruyne LA et al (2000) Gene transfer of virally encoded chemokine antagonists vMIP-II and MC148 prolongs cardiac allograft survival and inhibits donor-specific immunity. Gene Ther 7:575–582CrossRefPubMed

Stojanovic T et al (2002) Met-RANTES inhibition of mucosal perfusion failure in acute intestinal transplant rejection—role of endothelial cell-leukocyte interaction. J Vasc Res 39:51–58CrossRefPubMed

10.

Bedke J et al (2007) Anti-inflammatory effects of alphav integrin antagonism in acute kidney allograft rejection. Am J Pathol 171:1127–1139CrossRefPubMed

11.

Lee S (1967) An improved technique of renal transplantation in the rat. Surgery 61:771PubMed

12.

Klyscz T et al (1997) Cap image—a new kind of computer-assisted video image analysis system for dynamic capillary microscopy. Biomed Tech (Berl) 42:168–175CrossRef

13.

De Vriese AS et al (2000) Off-line analysis of red blood cell velocity in renal arterioles. J Vasc Res 37:26–31CrossRefPubMed

14.

Menger MD, Vollmar B (2000) Role of microcirculation in transplantation. Microcirculation 7:291–306PubMed

15.

Heuser M et al (2001) Differences in cortical microcirculation in the kidneys of unilaterally congenital hydronephrotic rats. Microvasc Res 62:172–178CrossRefPubMed

16.

Weber KS et al (2001) Selective recruitment of Th2-type cells and evasion from a cytotoxic immune response mediated by viral macrophage inhibitory protein-II. Eur J Immunol 31:2458–2466CrossRefPubMed

17.

Takami S et al (2001) Chemokine receptor antagonist peptide, viral MIP-II, protects the brain against focal cerebral ischemia in mice. J Cereb Blood Flow Metab 21:1430–1435CrossRefPubMed

18.

Ode-Hakim S et al (1996) Delayed-type hypersensitivity-like mechanisms dominate late acute rejection episodes in renal allograft recipients. Transplantation 61:1233–1240CrossRefPubMed

19.

Segerer S et al (2001) Expression of chemokines and chemokine receptors during human renal transplant rejection. Am J Kidney Dis 37:518–531CrossRefPubMed

20.

Nakano K et al (2003) Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded vMIP-I and vMIP-II induce signal transduction and chemotaxis in monocytic cells. Arch Virol 148:871–890CrossRefPubMed

21.

Rubant S et al (2006) Eukaryotic expression of the broad-spectrum chemokine receptor antagonist vMIP-II and its effects on T-cell function in vitro and in vivo. Exp Dermatol 15:634–642CrossRefPubMed

22.

Cugini D et al (2005) Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion. Kidney Int 67:1753–1761CrossRefPubMed

Title: Viral macrophage inflammatory protein-II improves acute rejection in allogeneic rat kidney transplants
Authors: Jens Bedke
Tomislav Stojanovic
Eva Kiss
Carl-Ludwig Behnes
Amanda E. Proudfoot
Hermann-Josef Gröne
Publication date: 01-08-2010
Publisher: Springer-Verlag
Published in: World Journal of Urology / Issue 4/2010
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-010-0556-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Viral macrophage inflammatory protein-II improves acute rejection in allogeneic rat kidney transplants

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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