Cloning and functional characterization of a novel human CC chemokine that binds to the CCR3 receptor and activates human eosinophils

John R. White*, Christina Imburgia, Edward Dul, Edward Appelbaum, Kevin O'Donnell, Daniel J. O'Shannessy, Mary Brawner, Jim Fornwald, John Adamou, Nabil A. Elshourbagy, Kate Kaiser, James J. Foley, Dulcie B. Schmidt, Kyung Johanson, Colin Macphee, Kitty Moores, Dean McNulty, Gilbert F. Scott, Robert P. Schleimer, Henry M. Sarau

*Corresponding author for this work

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Eotaxin has been found to bind exclusively to a single chemokine receptor, CCR3. Using expression sequence tag screening of an activated monocyte library, a second chemokine has been identified; it was expressed and purified from a Drosophila cell culture system and appears to only activate CCR3. Eotaxin-2, MPIF-2, or CKβ-6, is a human CC chemokine with low amino acid sequence identity to other chemokines. Eotaxin-2 promotes chemotaxis and Ca2+ mobilization in human eosinophils but not in neutrophils or monocytes. Cross-desensitization calcium mobilization experiments using purified eosinophils indicate that eotaxin and MCP-4, but not RANTES, MIP-1α, or MCP-3, can completely cross-desensitize the calcium response to eotaxin-2 on these cells, indicating that eotaxin-2 shares the same receptor used by eotaxin and MCP-4. Eotaxin-2 was the most potent eosinophil chemoattractant of all the chemokines tested. Eotaxin-2 also displaced 125I-eotaxin bound to the toned CCR3 stably expressed in CHO cells (CHO-CCR3) and to freshly isolated human eosinophils with affinities similar to eotaxin and MCP-4. 125I-Eotaxin-2 binds with high affinity to eosinophils and both eotaxin and cold eotaxin-2 displace the ligand with equal affinity. Eotaxin and eotaxin-2 promote a Ca2+ transient in RBL-2H3 cells stably transfected with CCR3 (RBL-2H3-CCR3) and both ligands cross- desensitized the response of the other but not the response to LTD4. The data indicate that eotaxin-2 is a potent eosinophil chemotactic chemokine exerting its activity solely through the CCR3 receptor.

Original languageEnglish (US)
Pages (from-to)667-675
Number of pages9
JournalJournal of Leukocyte Biology
Volume62
Issue number5
DOIs
StatePublished - Nov 1997

Keywords

  • Asthma
  • CCR3
  • CKβ- 6
  • Chemotaxis
  • EST
  • Eotaxin
  • Eotaxin-2
  • Expressed tag sequencing
  • MPIF-2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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