A Non-peptide Functional Antagonist of the CCR1 Chemokine Receptor Is Effective in Rat Heart Transplant Rejection

Richard Horuk*, Carol Clayberger, Alan M. Krensky, Zhaohui Wang, Hermann Josef Gröne, Christian Weber, Kim S C Weber, Peter J. Nelson, Karen May, Mary Rosser, Laura Dunning, Meina Liang, Brad Buckman, Ameen Ghannam, Howard P. Ng, Imadul Islam, John G. Bauman, Guo Ping Wei, Sean Monahan, Wei XuR. Michael Snider, Michael M. Morrissey, Joseph Hesselgesser, H. Daniel Perez

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Chemokines like RANTES appear to play a role in organ transplant rejection. Because RANTES is a potent agonist for the chemokine receptor CCR1, we examined whether the CCR1 receptor antagonist BX471 is efficacious in a rat heterotopic heart transplant rejection model. Treatment of animals with BX471 and a subtherapeutic dose of cyclosporin (2.5 mg/kg), which is by itself ineffective in prolonging transplant rejection, is much more efficacious in prolonging transplantation rejection than animals treated with either cyclosporin or BX471 alone. We have examined the mechanism of action of the CCR1 antagonist in in vitro flow assays over microvascular endothelium and have discovered that the antagonist blocks the firm adhesion of monocytes triggered by RANTES on inflamed endothelium. Together, these data demonstrate a significant role for CCR1 in allograft rejection.

Original languageEnglish (US)
Pages (from-to)4199-4204
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number6
DOIs
StatePublished - Feb 9 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'A Non-peptide Functional Antagonist of the CCR1 Chemokine Receptor Is Effective in Rat Heart Transplant Rejection'. Together they form a unique fingerprint.

Cite this