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1: J Biol Chem 2000 Oct 27; [epub ahead of print] Related Articles, Books, LinkOut
A non-peptide functional antagonist of the CCR1 chemokine receptor is effective in rat heart transplant rejection.
Horuk R, Clayberger C, Krensky AM, Wang Z, Grone HJ, Weber C, Weber KS, Nelson PJ, May K, Rosser M, Dunning L, Liang M, Buckman B, Ghannam A, Ng HP, Islam I, Bauman J, Wei GP, Monahan S, Xu W, Snider M, Morrissey MM, Hesselgesser J, Perez HD
Immunology, Berlex Biosciences, Richmond, CA 94804.
[Record supplied by publisher]
Chemokines like RANTES appear to play a role in organ transplant rejection. Since RANTES is a potent agonist for the chemokine receptor CCR1 we examined whether the CCR1 receptor antagonist BX 471 is efficacious in a rat heterotopic heart transplant rejection model. We find that animals treated with BX 471 and a sub therapeutic 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 BX 471 alone. We have examined the mechanism of action of the CCR1 antagonist in in vitro flow assays over microvascular endothelium and find 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.
PMID: 11054419 |
