Nature Immunology
3, 687 - 694 (2002)
Published online: 17 June 2002; | doi:10.1038/ni813
G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and
up-regulating CXCR4Isabelle Petit1, Martine Szyper-Kravitz2, Arnon Nagler3, Meir Lahav2, Amnon Peled4, Liliana Habler5, Tanya Ponomaryov1, Russell S. Taichman6, Fernando Arenzana-Seisdedos7, Nobutaka Fujii8, Judith Sandbank5, Dov Zipori1
& Tsvee Lapidot11
Departments of Immunology and Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. 2
Meir Medical Center, Kfar-Saba, Israel. 3
Sheba Medical Center, Tel Hashomer, Israel. 4
Hadassah University Hospital, Jerusalem, Israel. 5
Assaf Harofeh, Tsrifin Medical Center, Israel. 6
University of Michigan Dental School, Ann Arbor, MI, USA. 7
Unité d'Immunologie Virale, Institut Pasteur, Paris, France. 8
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Correspondence should be addressed to Tsvee Lapidot Tsvee.Lapidot@weizmann.ac.ilGranulocyte colony-stimulating factor (G-CSF)−induced hematopoietic stem cell mobilization is widely used for clinical transplantation; however, the mechanism is poorly understood. We report here that G-CSF induced a reduction of the chemokine stromal cell−derived factor 1 (SDF-1) and an increase in its receptor CXCR4 in the bone marrow (BM), whereas their protein expression in the blood was less affected. The gradual decrease of BM SDF-1, due mostly to its degradation by neutrophil elastase, correlated with stem cell mobilization. Elastase inhibition reduced both activities. Human and murine stem cell mobilization was inhibited by neutralizing CXCR4 or SDF-1 antibodies, demonstrating SDF-1−CXCR4 signaling in cell egress. We suggest that manipulation of SDF-1−CXCR4 interactions may be a means with which to control the navigation of progenitors between the BM and blood to improve the outcome of clinical stem cell transplantation.
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