| Literature DB >> 11054419 |
R Horuk1, C Clayberger, A M Krensky, Z Wang, H J Grone, C Weber, K S Weber, P J Nelson, K May, M Rosser, L Dunning, M Liang, B Buckman, A Ghannam, H P Ng, I Islam, J G Bauman, G P Wei, S Monahan, W Xu, R M Snider, M M Morrissey, J Hesselgesser, H D Perez.
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.Entities:
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Year: 2000 PMID： 11054419 DOI： 10.1074/jbc.M007457200
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157