The chemokine receptor antagonist AOP-RANTES reduces monocyte infiltration in experimental glomerulonephritis.
The chemokine receptor antagonist AOP-RANTES reduces monocyte infiltration in experimental glomerulonephritis.


BACKGROUND
This study was designed to evaluate the role of the novel chemokine receptor antagonist amino-oxypentane RANTES (AOP-RANTES), which blocks the binding of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and RANTES to the chemokine receptor-5 (CCR-5) on the infiltration of monocytes in experimental glomerulonephritis.


METHODS
Rats were treated twice daily with 12.5 microg AOP-RANTES following an induction of anti-rat-thymocyte antibody-mediated glomerulonephritis. The white blood cell count, glomerular monocyte infiltration, chemokine expression, and collagen type IV deposition were assessed.


RESULTS
The induction of glomerulonephritis increased glomerular monocyte/macrophage (M/M) infiltration at 24 hours and at 5 days was still higher than in controls. AOP-RANTES prevented glomerular M/M infiltration at 24 hours and at 5 days. This was paralleled by reduced glomerular collagen type IV deposition as a fibrotic marker in nephritic animals.


CONCLUSIONS
These data show that the CCR-5 chemokine receptor antagonist AOP-RANTES ameliorates M/M infiltration and improves glomerular pathology in experimental glomerulonephritis. The use of chemokine receptor antagonists may offer a new therapeutic option in inflammatory renal injuries.
Panzer
U
U
Department of Medicine, Division of Hamburg, University of Hamburg, Germany.
Schneider
A
A
Wilken
J
J
Thompson
D A
DA
Kent
S B
SB
Stahl
R A
RA
D000818:Animals; D019380:Anti-HIV Agents / Q000032:analysis / Q000494:pharmacology*; D015153:Blotting, Western; D065100:CCR5 Receptor Antagonists; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D003094:Collagen / Q000032:analysis; D015870:Gene Expression / Q000502:physiology; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology; D007678:Kidney Glomerulus / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D019713:Receptors, CCR5 / Q000235:genetics
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D012333:RNA, Messenger; D019713:Receptors, CCR5; C111989:aminooxypentane-RANTES; D003094:Collagen