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

Kidney Int. 1999 Dec;56(6):2107-15. doi: 10.1046/j.1523-1755.1999.00767.x.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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