A chimeric MIP-1α/RANTES protein demonstrates the use of different regions of the RANTES protein to bind and activate its receptors

• Published in: Journal of leukocyte biology Vol. 69; no. 6; pp. 977 - 985
• Main Authors: Blanpain, Cédric, Buser, Raphaële, Power, Christine A., Edgerton, Michael, Buchanan, Catherine, Mack, Matthias, Simmons, Graham, Clapham, Paul R., Parmentier, Marc, Proudfoot, Amanda E. I.
• Format: Journal Article
• Language: English
• Published: Society for Leukocyte Biology 01-06-2001
• Subjects: CCR1 protein; CCR3 protein; CCR4 protein; CCR5 protein; chemokine; ligand; macrophage inflammatory protein 1^a; monocyte; RANTES
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.69.6.977

Human RANTES (CCL5) and MIP‐1α (CCL3) bind and activate several CC chemokine receptors. RANTES is a high‐affinity ligand for CCR1 and CCR5, and it binds CCR3 with moderate affinity and CCR4 with low affinity. MIP‐1α has similar binding characteristics to RANTES except that it does not bind to CCR3. Here we have generated a chimera of human MIP‐1α and RANTES, called MIP/RANTES, consisting of the eight amino terminal residues of MIP‐1α preceding the CC motif, and the remainder of the sequence is RANTES. The chimera is able to induce chemotaxis of human monocytes. MIP/RANTES has >100‐fold reduction in binding to CCR1 and does not bind to CCR3 but retains full, functional binding to CCR5. It has equivalent affinity for CCR5 to MIP‐1α and RANTES, binding with an IC50 of 1.12 nM, and is able to mobilize calcium and induce endocytosis of CCR5 in PBMC in a manner equi‐potent to RANTES. It also retains the ability to inhibit R5 using HIV‐1 strains. Therefore, we conclude that the amino terminus of RANTES is not involved in CCR5 binding, but it is essential for CCR1 and CCR3.