CCR5 ligands modulate CXCL12-induced chemotaxis, adhesion, and Akt phosphorylation of human cord blood CD34+ cells

Sunanda Basu, Hal E. Broxmeyer

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

CXCL12 and its receptor CXCR4 play an important role in hematopoietic stem/progenitor cell (HSPC) migration from and retention within the bone marrow. HSPCs are very selective in their chemotactic response and undergo chemotaxis only in response to CXCL12. In addition to CXCR4, HSPCs express receptors for various other chemokines; however, the role of these receptors is not well understood. Freshly isolated CD34+ cells (highly enriched for HSPCs) from cord blood (CB) express low levels of CCR5; however, if the cells were washed with acidic buffer before Ab staining to remove any ligand bound to CCR5, then nearly 80% of CD34+ CB cells were found to express CCR5 on the cell surface. Although none of the CCR5 ligands investigated in this study (CCL3, CCL4, and CCL5) induced chemotaxis, at relatively high concentrations they transiently enhanced CXCL12-mediated chemotaxis of CD34+ CB cells. In contrast, CXCL12-mediated adhesion of cells to VCAM-1-coated surfaces was reduced if CD34+ CB cells were pretreated with these CCR5 ligands for 15 min. The effect of these chemokines on CXCL12-mediated responses was not at the level of CXCR4 expression, but on downstream signaling pathways elicited by CXCL12. Pretreatment with CCR5 chemokines enhanced CXCL12-mediated Akt phosphorylation, but down-modulated calcium flux in CD34+ CB cells. Modulation of CXCL12-mediated responses of CD34+ cells by CCR5 chemokines provides a possible mechanism that underlies movement of HSPCs during inflammation.

Original languageEnglish (US)
Pages (from-to)7478-7488
Number of pages11
JournalJournal of Immunology
Volume183
Issue number11
DOIs
StatePublished - Dec 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'CCR5 ligands modulate CXCL12-induced chemotaxis, adhesion, and Akt phosphorylation of human cord blood CD34<sup>+</sup> cells'. Together they form a unique fingerprint.

  • Cite this