The assignment of chemokine-chemokine receptor pairs: TARC and MIP-1 beta are not ligands for human CC-chemokine receptor 8. |
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Authors: | C G Garlisi H Xiao F Tian J A Hedrick M M Billah R W Egan S P Umland |
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Institution: | Allergy and Immunology, Schering-Plough Research Institute, Kenilworth 07033-0539, USA. charles.garlisi@spcorp.com |
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Abstract: | Identification of chemokine receptors and their associated ligands is crucial to the understanding of most immune reactions. Three human chemokines I-309, thymus and activation-regulated chemokine (TARC) and macrophage inflammatory protein-1beta (MIP-1beta)] have been reported to be ligands for CC-chemokine receptor 8 (CCR8). In this report, we present evidence that TARC and MIP-1beta did not bind to or induce chemotaxis through CCR8 on a stable transfected cell line (1D-21) and did not bind to CCR8 on in vitro differentiated human CD4(+) Th(2) cell cultures. Also, I-309-dependent calcium mobilization in 1D-21 cells and in Th(2) cells was desensitized by I-309 but not by MIP-1beta or TARC. These results provide strong evidence that, at physiologically relevant concentrations, I-309 is the only known human ligand for CCR8. These data also provide a framework for suggesting minimum requirements for the assignment of chemokine receptor-ligand pairs. |
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