The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/1/111/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 1, January 6, 1997 111-120

Articles

The Chemokine SDF-1 Is a Chemoattractant for Human CD34+ Hematopoietic Progenitor Cells and Provides a New Mechanism to Explain the Mobilization of CD34+ Progenitors to Peripheral Blood

A. Aiuti*,{ddagger}, I.J. Webb||,¶, C. Bleul{ddagger}, T. Springer{ddagger}, and J.C. Gutierrez-Ramos*,{ddagger},**

From the * Center for Blood Research, Inc., and the {ddagger} Department of Genetics, § Department of Pathology, and || Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115; Blood Component Laboratory, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and ** Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139

Hematopoietic progenitor cells migrate in vitro and in vivo towards a gradient of the chemotactic factor stromal cell-derived factor-1 (SDF-1) produced by stromal cells. This is the first chemoattractant reported for human CD34+ progenitor cells. Concentrations of SDF-1 that elicit chemotaxis also induce a transient elevation of cytoplasmic calcium in CD34+ cells. SDF-1-induced chemotaxis is inhibited by pertussis toxin, suggesting that its signaling in CD34+ cells is mediated by seven transmembrane receptors coupled to Gi proteins. CD34+ cells migrating to SDF-1 include cells with a more primitive (CD34+/CD38– or CD34+/DR–) phenotype as well as CD34+ cells phenotypically committed to the erythroid, lymphoid and myeloid lineages, including functional BFU-E, CFU-GM, and CFU-MIX progenitors. Chemotaxis of CD34+ cells in response to SDF-1 is increased by IL-3 in vitro and is lower in CD34+ progenitors from peripheral blood than in CD34+ progenitors from bone marrow, suggesting that an altered response to SDF-1 may be associated with CD34 progenitor mobilization.

Address correspondence to J.C. Gutierrez-Ramos, Millenium Pharmaceuticals, Inc., 640 Memorial Drive, Cambridge, MA 02139-4815.

The authors are indebted to Dr. Van Etten for critical reading of this manuscript and to Drs. Arman, Alvarez de Mon, and Alvarez for their efforts in locating invaluable PBPC and BM samples. We thank especially Dr. Anderson for helpful discussions and Drs. Mazo and Gerwin for their help.

This work has been funded by National Institutes of Health grants HL 148675-02 and HL94-10-B, and by the Aplastic Foundation of America grants CiCyT PB93-0317. J.C. Gutierrez-Ramos is the Amy C. Potter fellow. A. Aiuti's present address is TIGET, Instituto Scientifico San Raffaele, Via Olgettima 58, 20132, Milano, Italy.

1Abbreviations used in this paper: BM, bone marrow; CFC, colony-forming cell; FL, fetal liver; G-CSF, granulocyte–colony-stimulating factor; HPC, hematopoietic progenitor cells; HS, Hepes-buffered saline; MCP, macrophage chemotactic protein; MIP, macrophage inflammatory protein; PBPC, peripheral blood progenitor cell; PI, propidium iodide; SDF, stromal cell-derived factor.


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