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Blood, 13 August 2009, Vol. 114, No. 7, pp. 1331-1339. Prepublished online as a Blood First Edition Paper on January 13, 2009; DOI 10.1182/blood-2008-10-184754. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-10-184754v1 114/7/1331    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 Google Scholar Articles by Christopher, M. J. Articles by Link, D. C. PubMed PubMed Citation Articles by Christopher, M. J. Articles by Link, D. C. Related Collections Hematopoiesis and Stem Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization Matthew J. Christopher1, Fulu Liu1, Matthew J. Hilton2, Fanxin Long2, and Daniel C. Link1 1 Division of Oncology, Department of Medicine, and 2 Departments of Medicine and Developmental Biology, Washington University School of Medicine, St Louis, MO Current evidence suggests that hematopoietic stem/progenitor cell (HSPC) mobilization by granulocyte colony-stimulating factor (G-CSF) is mediated by induction of bone marrow proteases, attenuation of adhesion molecule function, and disruption of CXCL12/CXCR4 signaling in the bone marrow. The relative importance and extent to which these pathways overlap or function independently are uncertain. Despite evidence of protease activation in the bone marrow, HSPC mobilization by G-CSF or the chemokine Groβ was abrogated in CXCR4–/– bone marrow chimeras. In contrast, HSPC mobilization by a VLA-4 antagonist was intact. To determine whether other mobilizing cytokines disrupt CXCR4 signaling, we characterized CXCR4 and CXCL12 expression after HSPC mobilization with Flt3 ligand (Flt3L) and stem cell factor (SCF). Indeed, treatment with Flt3L or SCF resulted in a marked decrease in CXCL12 expression in the bone marrow and a loss of surface expression of CXCR4 on HSPCs. RNA in situ and sorting experiments suggested that the decreased CXCL12 expression is secondary to a loss of osteoblast lineage cells. Collectively, these data suggest that disruption of CXCR4 signaling and attenuation of VLA-4 function are independent mechanisms of mobilization by G-CSF. Loss of CXCL12 expression by osteoblast appears to be a common and key step in cytokine-induced mobilization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: HSC mobilization: new incites and insights Jason Ross and Linheng Li Blood 2009 114: 1283-1284. [Full Text] [PDF] This article has been cited by other articles: J. Ross and L. Li HSC mobilization: new incites and insights Blood, August 13, 2009; 114(7): 1283 - 1284. [Full Text] [PDF]

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