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.
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.
Kim
C H
CH
Department of Microbiology/Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202, USA.
Broxmeyer
H E
HE
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
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