A non-peptide functional antagonist of the CCR1 chemokine receptor is effective in rat heart transplant rejection

Citation
R. Horuk et al., A non-peptide functional antagonist of the CCR1 chemokine receptor is effective in rat heart transplant rejection, J BIOL CHEM, 276(6), 2001, pp. 4199-4204
Citations number
22
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
276
Issue
6
Year of publication
2001
Pages
4199 - 4204
Database
ISI
SICI code
0021-9258(20010209)276:6<4199:ANFAOT>2.0.ZU;2-3
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 exa mined whether the CCR1 receptor antagonist BX471 is efficacious in a rat he terotopic heart transplant rejection model. Treatment of animals with BX471 and a subtherapeutic dose of cyclosporin (2.5 mg/kg), which is by itself i neffective in prolonging transplant rejection, is much more efficacious in prolonging transplantation rejection than animals treated with either cyclo sporin 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 trigg ered by RANTES on inflamed endothelium. Together, these data demonstrate a significant role for CCR1 in allograft rejection.