Binding and Functional Properties of Recombinant and Endogenous CXCR3 Chemokine Receptors

• Published in: The Journal of biological chemistry 1998-07, Vol.273 (29), p.18288-18291
• Main Authors: Weng, Y, Siciliano, S J, Waldburger, K E, Sirotina-Meisher, A, Staruch, M J, Daugherty, B L, Gould, S L, Springer, M S, DeMartino, J A
• Format: Article
• Language: English
• Subjects: Animals; Chemokine CCL11; Chemokine CCL5 - metabolism; Chemokine CCL7; Chemokine CXCL10; Chemokine CXCL9; Chemokines, CC; Chemokines, CXC - metabolism; Chemotactic Factors, Eosinophil - metabolism; CHO Cells; Cloning, Molecular; Cricetinae; Cytokines - metabolism; Humans; Intercellular Signaling Peptides and Proteins; Interferon-gamma - pharmacology; Lymphocyte Activation; Monocyte Chemoattractant Proteins - metabolism; Protein Binding; Receptors, Chemokine - metabolism; Receptors, CXCR3; Receptors, Cytokine - metabolism; Recombinant Proteins - metabolism; T-Lymphocytes - metabolism; Up-Regulation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.29.18288

IP10 and MIG are two members of the CXC branch of the chemokine superfamily whose expression is dramatically up-regulated by interferon (IFN)-γ. The proteins act largely on natural killer (NK)-cells and activated T-cells and have been implicated in mediating some of the effects of IFN-γ and lipopolysaccharides (LPSs), as well as T-cell-dependent anti-tumor responses. Recently both chemokines have been shown to be functional agonists of the same G-protein-coupled receptor, CXCR3. We now report the pharmacological characterization of CXCR3 and find that, when heterologously expressed, CXCR3 binds IP10 and MIG with K i values of 0.14 and 4.9 n m , respectively. The receptor has very modest affinity for SDF-1α and little or no affinity for other CXC-chemokines. The properties of the endogenous receptor expressed on activated T-cells are similar. Surprisingly, several CC-chemokines, particularly eotaxin and MCP-4, also compete with moderate affinity for the binding of IP10 to CXCR3. Eotaxin does not activate CXCR3 but, in CXCR3-transfected cells, can block IP10-mediated receptor activation. Eotaxin, therefore, may be a natural CXCR3 antagonist.