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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4478-4486. Prepublished online as a Blood First Edition Paper on February 26, 2004; DOI 10.1182/blood-2003-03-0875. This Article Full Text (PDF) All Versions of this Article: 2003-03-0875v1 103/12/4478    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kimura, T. Articles by Mohle, R. Search for Related Content PubMed PubMed Citation Articles by Kimura, T. Articles by Mohle, R. Social Bookmarking                   What's this? Submitted March 21, 2003 Accepted February 15, 2004 The sphingosine 1-phosphate (S1P) receptor agonist FTY720 supports CXCR4-dependent migration and bone marrow homing of human CD34+ progenitor cells Takafumi Kimura, Andreas M Boehmler, Gabriele Seitz, Selim Kuci, Tina Wiesner, Volker Brinkmann, Lothar Kanz, and Robert Mohle* Dept. of Medicine II, Univ. of Tubingen, Tubingen, Germany Children's Hospital, Univ. of Tubingen, Tubingen, Germany Novartis Institutes for Biomedical Research, Basel, Switzerland * Corresponding author; email: robert.moehle{at}med.uni-tuebingen.de. The novel immunosuppressant FTY720 activates sphingosine 1-phosphate receptors (S1PRs) that affect responsiveness of lymphocytes to chemokines such as SDF-1, resulting in increased lymphocyte homing to secondary lymphoid organs. Since SDF-1 and its receptor CXCR4 are also involved in bone marrow (BM) homing of hematopoietic stem and progenitor cells (HPC), we analyzed expression of S1PRs and the influence of FTY720 on SDF-1/CXCR4-mediated effects in human HPC. By RT-PCR, S1PRs were expressed in mobilized CD34+ HPC, particularly in primitive CD34+/CD38- cells. Incubation of HPC with FTY720 resulted in prolonged SDF-1-induced calcium mobilization and actin polymerisation, and substantially increased SDF-1-dependent in vitro transendothelial migration, without affecting VLA-4, VLA-5 and CXCR4 expression. In NOD/SCID mice, the number of CD34+/CD38- cells that homed to the BM after 18 h was significantly raised by pretreatment of animals and cells with FTY720, tending to result in improved engraftment. In addition, in vitro growth of HPC (week 5 CAFC) was 2.4-fold increased. We conclude that activation of S1PRs by FTY720 increases CXCR4 function in HPC both in vitro and in vivo, supporting homing and proliferation of HPC. In the hematopoietic microenvironment, S1PRs are involved in migration and maintenance of HPC by modulating the effects of SDF-1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Boehmler, A. Drost, L. Jaggy, G. Seitz, T. Wiesner, C. Denzlinger, L. Kanz, and R. Mohle The CysLT1 Ligand Leukotriene D4 Supports {alpha}4{beta}1- and {alpha}5{beta}1-Mediated Adhesion and Proliferation of CD34+ Hematopoietic Progenitor Cells J. Immunol., June 1, 2009; 182(11): 6789 - 6798. [Abstract] [Full Text] [PDF] K. Gossens, S. Naus, S. Y. Corbel, S. Lin, F. M.V. Rossi, J. Kast, and H. J. Ziltener Thymic progenitor homing and lymphocyte homeostasis are linked via S1P-controlled expression of thymic P-selectin/CCL25 J. Exp. Med., April 13, 2009; 206(4): 761 - 778. 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