Viral macrophage inflammatory protein-II improves acute rejection in allogeneic rat kidney transplants.
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.
Bedke
Jens
J
Department of Urology, Eberhard Karls University Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany. bedke@live.com
Stojanovic
Tomislav
T
Kiss
Eva
E
Behnes
Carl-Ludwig
CL
Proudfoot
Amanda E
AE
Gröne
Hermann-Josef
HJ
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
D000893:Anti-Inflammatory Agents; D018925:Chemokines; C108059:vMIP-II
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