title: 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.
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.
authors.affiliation: Department of Microbiology/Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Kim
authors.forename: H E
authors.initials: HE
authors.lastname: Broxmeyer
mesh_terms: D000199:Actins / Q000737:chemistry; D001704:Biopolymers; D002455:Cell Division / Q000187:drug effects; D054421:Chemokine CCL21; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D018925:Chemokines / Q000494:pharmacology*; D019742:Chemokines, CC / Q000494:pharmacology*; D019743:Chemokines, CXC / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4 / Q000187:drug effects* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000199:Actins; D001704:Biopolymers; C515478:CCL21 protein, human; C515370:CCR7 protein, human; C111954:CXC chemokine Mig; C515255:CXCL12 protein, human; C515187:CXCR3 protein, human; D054421:Chemokine CCL21; D054357:Chemokine CXCL10; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D054400:Receptors, CCR7; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D011994:Recombinant Proteins