SLC/exodus2/6Ckine/TCA4 Induces Chemotaxis of Hematopoietic Progenitor Cells: Differential Activity of Ligands of CCR7, CXCR3, or CXCR4 in Chemotaxis vs. Suppression of Progenitor Proliferation

J Leukoc Biol. 1999 Sep;66(3):455-61. doi: 10.1002/jlb.66.3.455.

Abstract

Chemokines induce chemotaxis of hematopoietic progenitor cells (HPC), and suppress their proliferation. In this study we report that SLC/ Exodus2/6Ckine/TCA4 (hereafter termed SLC) is a chemoattractant for human CD34+ HPC. SLC mainly induces preferential chemotaxis of macrophage progenitors. We examined the chemotactic activity of CXCR3 ligands on CD34+ HPC because it has been reported that SLC is a potential ligand of CXC chemokine receptor, CXCR3, in addition to a CC chemokine receptor, CCR7. It was found that the CXCR3 ligands, MIG and interferon-gamma inducible protein-10 (IP-10), unlike SLC, did not induce chemotaxis of CD34+ HPC. In this regard, CCR7 ligands (SLC and CKbeta-11), but not IP-10 and MIG, induce actin polymerization in CD34+ cells. On the other hand, CCR7 ligands and CXCR3 ligands, but not the CXCR4 ligand SDF-1, showed inhibitory activity for proliferation of myeloid progenitor cells. Our results suggest that SLC is a potential trafficking factor for HPC, and that chemokines that bind CCR7, CXCR4, and CXCR3 have differential biological activities on HPC in terms of suppression and chemotaxis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / chemistry
  • Biopolymers
  • Cell Division / drug effects
  • Chemokine CCL21
  • Chemokine CXCL10
  • Chemokine CXCL12
  • Chemokine CXCL9
  • Chemokines / pharmacology*
  • Chemokines, CC / pharmacology*
  • Chemokines, CXC / pharmacology
  • Chemotactic Factors / pharmacology*
  • Chemotaxis / drug effects*
  • Colony-Forming Units Assay
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Receptors, CCR7
  • Receptors, CXCR3
  • Receptors, CXCR4 / drug effects*
  • Receptors, CXCR4 / metabolism
  • Receptors, Chemokine / drug effects*
  • Receptors, Chemokine / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Actins
  • Biopolymers
  • CCL21 protein, human
  • CCR7 protein, human
  • CXC chemokine Mig
  • CXCL12 protein, human
  • CXCR3 protein, human
  • Chemokine CCL21
  • Chemokine CXCL10
  • Chemokine CXCL12
  • Chemokine CXCL9
  • Chemokines
  • Chemokines, CC
  • Chemokines, CXC
  • Chemotactic Factors
  • Receptors, CCR7
  • Receptors, CXCR3
  • Receptors, CXCR4
  • Receptors, Chemokine
  • Recombinant Proteins