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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3928-3937. Prepublished online as a Blood First Edition Paper on August 15, 2006; DOI 10.1182/blood-2006-02-006353. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-02-006353v1 108/12/3928    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Pello, O. M. Articles by Mellado, M. Search for Related Content PubMed PubMed Citation Articles by Pello, O. M. Articles by Mellado, M. Related Collections Signal Transduction Stem Cells in Hematology Hematopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  STEM CELLS IN HEMATOLOGY SOCS up-regulation mobilizes autologous stem cells through CXCR4 blockade Oscar M. Pello, María del Carmen Moreno-Ortiz, José Miguel Rodríguez-Frade, Laura Martínez-Muñoz, Daniel Lucas, Lucio Gómez, Pilar Lucas, Enrique Samper, Miguel Aracil, Carlos Martínez-A, Antonio Bernad, and Mario Mellado From the Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain. The chemokine CXCL12 influences self-renewal and differentiation of hematopoietic stem cell precursors in bone marrow by directing them toward specific stromalcell components. CXCL12 up-regulates members of the SOCS family through JAK/STAT activation, a mechanism that attenuates chemokine responses. SOCS expression may thus modulate retention of hematopoietic precursors (Sca-1+ c-Kit+Lin– cells) in bone marrow. We show that in bovine growth hormone transgenic mice and in growth hormone–treated mice, SOCS up-regulation correlated with a large number of Sca-1+ c-Kit+Lin– cells in blood. Retroviral transduction of SOCSs blocked in vitro migration of Sca-1+c-Kit+Lin– cells, as well as their capacity to reconstitute lethally irradiated mice. Furthermore, in lethally irradiated mice reconstituted with bone marrow infected by a tetracycline-regulated, SOCS-expressing lentiviral vector, doxycycline treatment promoted rapid, extensive precursor mobilization to the periphery. The results indicate that by blocking CXCR4-mediated functions, SOCSs modulate hematopoietic precursor cell retention in bone marrow, and suggest the therapeutic interest of SOCS manipulation in several pathologic situations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C.-R. Yu, R. M. Mahdi, X. Liu, A. Zhang, T. Naka, T. Kishimoto, and C. E. Egwuagu SOCS1 Regulates CCR7 Expression and Migration of CD4+ T Cells into Peripheral Tissues J. Immunol., July 15, 2008; 181(2): 1190 - 1198. [Abstract] [Full Text] [PDF] Y. J. Cao, C. W. Flexner, S. Dunaway, J.-G. Park, K. Klingman, I. Wiggins, J. Conley, C. Radebaugh, A. D. Kashuba, R. MacFarland, et al. Effect of Low-Dose Ritonavir on the Pharmacokinetics of the CXCR4 Antagonist AMD070 in Healthy Volunteers Antimicrob. Agents Chemother., May 1, 2008; 52(5): 1630 - 1634. [Abstract] [Full Text] [PDF]

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