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

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 G(i) 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.