title: Viral macrophage inflammatory protein-II improves acute rejection in allogeneic rat kidney transplants.
abstract: OBJECTIVE
  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 x 15 microg or 100 microg/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.
authors.affiliation: Department of Urology, Eberhard Karls University Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany. bedke@live.com
authors.forename: Jens
authors.initials: J
authors.lastname: Bedke
authors.forename: Tomislav
authors.initials: T
authors.lastname: Stojanovic
authors.forename: Eva
authors.initials: E
authors.lastname: Kiss
authors.forename: Carl-Ludwig
authors.initials: CL
authors.lastname: Behnes
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D018925:Chemokines / Q000494:pharmacology*; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012079:Renal Circulation / Q000187:drug effects; D014184:Transplantation, Homologous
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; C108059:vMIP-II
references.citation: Transplantation. 2008 Jun 15;85(11):1640-7
references.pmid: 18551072
references.citation: Am J Kidney Dis. 2001 Mar;37(3):518-31
references.pmid: 11228176
references.citation: Eur J Immunol. 2001 Aug;31(8):2458-66
references.pmid: 11500830
references.citation: Transplantation. 1996 Apr 27;61(8):1233-40
references.pmid: 8610424
references.citation: Curr Opin Immunol. 2003 Oct;15(5):479-86
references.pmid: 14499253
references.citation: J Vasc Res. 2002 Jan-Feb;39(1):51-8
references.pmid: 11844937
references.citation: Cell. 1994 Jan 28;76(2):301-14
references.pmid: 7507411
references.citation: Arch Virol. 2003 May;148(5):871-90
references.pmid: 12721796
references.citation: Biomed Tech (Berl). 1997 Jun;42(6):168-75
references.pmid: 9312307
references.citation: Microvasc Res. 2001 Sep;62(2):172-8
references.pmid: 11516246
references.citation: Gene Ther. 2000 Apr;7(7):575-82
references.pmid: 10819572
references.citation: FASEB J. 1999 Aug;13(11):1371-83
references.pmid: 10428761
references.citation: J Vasc Res. 2000 Jan-Feb;37(1):26-31
references.pmid: 10720883
references.citation: Transplantation. 2001 Oct 15;72(7):1195-7
references.pmid: 11602841
references.citation: J Cereb Blood Flow Metab. 2001 Dec;21(12):1430-5
references.pmid: 11740204
references.citation: Microcirculation. 2000 Oct;7(5):291-306
references.pmid: 11079248
references.citation: Am J Transplant. 2007 Mar;7(3):527-37
references.pmid: 17229070
references.citation: Kidney Int. 2005 May;67(5):1753-61
references.pmid: 15840022
references.citation: J Exp Med. 1998 Jul 6;188(1):193-8
references.pmid: 9653095
references.citation: Am J Pathol. 2007 Oct;171(4):1127-39
references.pmid: 17702892
references.citation: Exp Dermatol. 2006 Aug;15(8):634-42
references.pmid: 16842602
references.citation: Surgery. 1967 May;61(5):771-3
references.pmid: 5337423