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S1P(1) overexpression stimulates S1P-dependent chemotaxis of human CD34+ hematopoietic progenitor cells but strongly inhibits SDF-1/CXCR4-dependent migration and in vivo homing.
Mol Immunol. 2008 Nov; 46(1):166-71.MI

Abstract

The CXC chemokine receptor 4 (CXCR4) and its ligand stromal derived factor 1 (SDF-1) regulate egress and homing of hematopoietic stem cells. Activation of sphingosine-1-phosphate (S1P) receptors (S1P(1-5)) modulates chemokine-induced migration of lymphocytes and hematopoietic stem cells. To analyze the influence of S1P(1) on SDF-1-dependent chemotaxis and trafficking, we overexpressed S1P(1) in CD34+ mobilized peripheral blood progenitor cells (PBPCs). Using a gamma-retroviral vector, transgene overexpression was achieved in more than 90% of target cells. S1P(1) transgene positive PBPCs showed enhanced chemotaxis towards S1P. S1P(1) overexpression resulted in reduced CXCR4 surface expression levels and strong inhibition of SDF-1-dependent ERK1/2 phosphorylation and Ca(2+) flux. Furthermore, SDF-1-dependent migration of S1P(1) overexpressing PBPCs or Jurkat cells was reduced up to 10-fold. Sublethally irradiated NOD/SCID mice were transplanted with 6-day cultured PBPCs overexpressing either S1P(1)-IRES-GFP or GFP alone. Screening for GFP positive human cells in the mouse bone marrow 20h after transplantation revealed an eightfold reduction in bone marrow homing of S1P(1) transgene expressing cells. Our data suggest that S1P(1) acts as an inhibitor of CXCR4-dependent migration of hematopoietic cells to sites of SDF-1 production.

Authors+Show Affiliations

Department of Pediatrics, University Clinic Dresden, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18760838

Citation

Ryser, Martin F., et al. "S1P(1) Overexpression Stimulates S1P-dependent Chemotaxis of Human CD34+ Hematopoietic Progenitor Cells but Strongly Inhibits SDF-1/CXCR4-dependent Migration and in Vivo Homing." Molecular Immunology, vol. 46, no. 1, 2008, pp. 166-71.
Ryser MF, Ugarte F, Lehmann R, et al. S1P(1) overexpression stimulates S1P-dependent chemotaxis of human CD34+ hematopoietic progenitor cells but strongly inhibits SDF-1/CXCR4-dependent migration and in vivo homing. Mol Immunol. 2008;46(1):166-71.
Ryser, M. F., Ugarte, F., Lehmann, R., Bornhäuser, M., & Brenner, S. (2008). S1P(1) overexpression stimulates S1P-dependent chemotaxis of human CD34+ hematopoietic progenitor cells but strongly inhibits SDF-1/CXCR4-dependent migration and in vivo homing. Molecular Immunology, 46(1), 166-71. https://doi.org/10.1016/j.molimm.2008.07.016
Ryser MF, et al. S1P(1) Overexpression Stimulates S1P-dependent Chemotaxis of Human CD34+ Hematopoietic Progenitor Cells but Strongly Inhibits SDF-1/CXCR4-dependent Migration and in Vivo Homing. Mol Immunol. 2008;46(1):166-71. PubMed PMID: 18760838.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - S1P(1) overexpression stimulates S1P-dependent chemotaxis of human CD34+ hematopoietic progenitor cells but strongly inhibits SDF-1/CXCR4-dependent migration and in vivo homing. AU - Ryser,Martin F, AU - Ugarte,Fernando, AU - Lehmann,Romy, AU - Bornhäuser,Martin, AU - Brenner,Sebastian, Y1 - 2008/08/29/ PY - 2008/02/24/received PY - 2008/07/11/revised PY - 2008/07/15/accepted PY - 2008/9/2/pubmed PY - 2009/4/9/medline PY - 2008/9/2/entrez SP - 166 EP - 71 JF - Molecular immunology JO - Mol Immunol VL - 46 IS - 1 N2 - The CXC chemokine receptor 4 (CXCR4) and its ligand stromal derived factor 1 (SDF-1) regulate egress and homing of hematopoietic stem cells. Activation of sphingosine-1-phosphate (S1P) receptors (S1P(1-5)) modulates chemokine-induced migration of lymphocytes and hematopoietic stem cells. To analyze the influence of S1P(1) on SDF-1-dependent chemotaxis and trafficking, we overexpressed S1P(1) in CD34+ mobilized peripheral blood progenitor cells (PBPCs). Using a gamma-retroviral vector, transgene overexpression was achieved in more than 90% of target cells. S1P(1) transgene positive PBPCs showed enhanced chemotaxis towards S1P. S1P(1) overexpression resulted in reduced CXCR4 surface expression levels and strong inhibition of SDF-1-dependent ERK1/2 phosphorylation and Ca(2+) flux. Furthermore, SDF-1-dependent migration of S1P(1) overexpressing PBPCs or Jurkat cells was reduced up to 10-fold. Sublethally irradiated NOD/SCID mice were transplanted with 6-day cultured PBPCs overexpressing either S1P(1)-IRES-GFP or GFP alone. Screening for GFP positive human cells in the mouse bone marrow 20h after transplantation revealed an eightfold reduction in bone marrow homing of S1P(1) transgene expressing cells. Our data suggest that S1P(1) acts as an inhibitor of CXCR4-dependent migration of hematopoietic cells to sites of SDF-1 production. SN - 0161-5890 UR - https://www.unboundmedicine.com/medline/citation/18760838/S1P_1__overexpression_stimulates_S1P_dependent_chemotaxis_of_human_CD34+_hematopoietic_progenitor_cells_but_strongly_inhibits_SDF_1/CXCR4_dependent_migration_and_in_vivo_homing_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(08)00296-4 DB - PRIME DP - Unbound Medicine ER -