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- Title
The chemokine receptor antagonist AOP-RANTES reduces monocyte infiltration in experimental glomerulonephritis.
- Authors
Panzer, Ulf; Schneider, André; Wilken, Jill; Thompson, Darren A.; Kent, Stephen B.H.; Stahl, Rolf A.K.
- Abstract
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-1α (MIP-1α), MIP-1β, 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 μg 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. Conclusion. 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.
- Subjects
GLOMERULONEPHRITIS; CHEMOKINES; IMMUNOLOGY
- Publication
Kidney International, 1999, Vol 56, Issue 6, p2107
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.1999.00767.x