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

Abstract

UNLABELLED:

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.

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.

• Authors: U Panzer, A Schneider, J Wilken, D A Thompson, S B Kent, R A Stahl
• Journal: Kidney international (Kidney Int) Vol. 56 Issue 6 Pg. 2107-15 (Dec 1999) ISSN: 0085-2538 [Print] United States
• PMID: 10594786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• CCR5 Receptor Antagonists
• Chemokine CCL2
• Chemokine CCL5
• RNA, Messenger
• Receptors, CCR5
• aminooxypentane-RANTES
• Collagen

Topics

• Animals
• Anti-HIV Agents (analysis, pharmacology)
• Blotting, Western
• CCR5 Receptor Antagonists
• Chemokine CCL2 (analysis, genetics, metabolism)
• Chemokine CCL5 (analogs & derivatives, analysis, pharmacology)
• Collagen (analysis)
• Gene Expression (physiology)
• Glomerulonephritis (drug therapy, immunology)
• Kidney Glomerulus (chemistry, cytology, immunology)
• Leukocyte Count
• Male
• Monocytes (drug effects, immunology, metabolism)
• RNA, Messenger (analysis)
• Rats
• Rats, Wistar
• Receptors, CCR5 (genetics)