Ckβ-11/macrophage inflammatory protein-3β/EBI1-ligand chemokine is an efficacious chemoattractant for T and B cells

Chang H. Kim, Louis M. Pelus, John R. White, Edward Applebaum, Kyung Johanson, Hal E. Broxmeyer

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

We examined the functional properties of CKβ-11/MIP-3β/ELC, a recently reported CC chemokine that specifically binds to a chemokine receptor, EBI1/BLR2/CCR7. CKβ-11/MIP-3β/ELC is distantly related to other CC and CXC chemokines in primary amino acid sequence structure. Recombinant human CKβ- 11/MIP-3β/ELC expressed from a mammalian cell system showed potent chemotactic activity for T cells and B cells but not for granulocytes and monocytes. An optimal concentration of CKβ-11/MIP-3β/ELC attracted most input T cells within 3 h, a chemotactic activity comparable with that of stromal cell derived factor 1 (SDF-1), a highly efficacious CXC chemokine. CKβ-11/MIP-3β/ELC equally attracted naive CD45RA+ and memory type CD45RO+ T cells. CKβ-11/MIP-3β/ELC also strongly attracted both CD4+ and CD8+ T cells, but the attraction for CD4+ T cells was greater. CKβ-11/MIP-3β/ELC was also a more efficacious chemoattractant for B cells than MIP-1α, a known B cell chemoattractant. CKβ-11/MIP-3β/ELC induced actin polymerization in lymphocytes, and chemotaxis was completely blocked by pertussis toxin showing its receptor, most likely EBI1/BLR2/CCR7, is coupled to a G(αd) protein. CKβ-11/MIP-3β/ELC induced calcium mobilization in lymphocytes, which could be desensitized by SDF-1, suggesting possible cross-regulation in their signaling. Human CKβ-11/MIP-3β/ELC attracted murine splenocytes suggesting functional conservation of CKβ-11/MIP-3β/ELC between human and mouse. The efficacy of chemoattraction by CKβ-11/MIP-3β/ELC and tissue expression of its mRNA suggest that CKβ-11/MIP-3β/ELC may be important in trafficking of T cells in thymus, and T cell and B cell migration to secondary lymphoid organs.

Original languageEnglish (US)
Pages (from-to)2418-2424
Number of pages7
JournalJournal of Immunology
Volume160
Issue number5
StatePublished - Mar 1 1998

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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