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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.

Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC - J. Exp. Med. (1997)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Blood Research, Inc., Boston, Massachusetts, USA.

ABSTRACT
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.

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Cytokine modulation of CD34+ cell chemotaxis to SDF-1.  CD34+ cells were incubated for 18 h in the presence of either 30 ng/ml  IL-3, 50 ng/ml G-CSF or 100 ng/ml SCF and assayed for transendothelial chemotaxis in response to 300 ng/ml of SDF-1. Results show the  mean fold change in the chemotactic response of CD34+ in three separate  experiments performed in duplicate, with respect to chemotaxis before  treatment (*P <0.05).
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Figure 5: Cytokine modulation of CD34+ cell chemotaxis to SDF-1. CD34+ cells were incubated for 18 h in the presence of either 30 ng/ml IL-3, 50 ng/ml G-CSF or 100 ng/ml SCF and assayed for transendothelial chemotaxis in response to 300 ng/ml of SDF-1. Results show the mean fold change in the chemotactic response of CD34+ in three separate experiments performed in duplicate, with respect to chemotaxis before treatment (*P <0.05).

Mentions: Several cytokines, including IL-3, SCF, G-CSF, and GM-CSF are known to mobilize hematopoietic progenitors to the peripheral blood (45). In view of the finding described above that G-CSF-mobilized CD34+ progenitors showed a reduced chemotactic response to SDF-1, we studied whether this and other cytokines were able to modify the response of CD34+ cells to SDF-1 in vitro. These experiments also possibly concern procedures such as the stimulation of CD34+ cells with cytokines in vitro, which is essential for ex vivo survival and/or expansion of HPC before transplantation (46–48), or the current use of cytokines for facilitating retroviral-mediated gene transfer into HPC (49). We tested whether an incubation for 18 h with either IL-3, SCF, or G-CSF affected the chemotaxis of human BM CD34+ cells to SDF-1 (Fig. 5). IL-3 induced a significant increase (2.2 fold) in the percentage of cells responding to SDF-1. Incubation of CD34+ cells with SCF or G-CSF resulted in increased chemotaxis of these cells to SDF-1 (1.4- to 1.9-fold), but which did not reach statistical significance. A similar increase in chemotactic activity after exposure to IL-3 was observed using PB CD34+ cells (data not shown).


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.

Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC - J. Exp. Med. (1997)

Cytokine modulation of CD34+ cell chemotaxis to SDF-1.  CD34+ cells were incubated for 18 h in the presence of either 30 ng/ml  IL-3, 50 ng/ml G-CSF or 100 ng/ml SCF and assayed for transendothelial chemotaxis in response to 300 ng/ml of SDF-1. Results show the  mean fold change in the chemotactic response of CD34+ in three separate  experiments performed in duplicate, with respect to chemotaxis before  treatment (*P <0.05).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196104&req=5

Figure 5: Cytokine modulation of CD34+ cell chemotaxis to SDF-1. CD34+ cells were incubated for 18 h in the presence of either 30 ng/ml IL-3, 50 ng/ml G-CSF or 100 ng/ml SCF and assayed for transendothelial chemotaxis in response to 300 ng/ml of SDF-1. Results show the mean fold change in the chemotactic response of CD34+ in three separate experiments performed in duplicate, with respect to chemotaxis before treatment (*P <0.05).
Mentions: Several cytokines, including IL-3, SCF, G-CSF, and GM-CSF are known to mobilize hematopoietic progenitors to the peripheral blood (45). In view of the finding described above that G-CSF-mobilized CD34+ progenitors showed a reduced chemotactic response to SDF-1, we studied whether this and other cytokines were able to modify the response of CD34+ cells to SDF-1 in vitro. These experiments also possibly concern procedures such as the stimulation of CD34+ cells with cytokines in vitro, which is essential for ex vivo survival and/or expansion of HPC before transplantation (46–48), or the current use of cytokines for facilitating retroviral-mediated gene transfer into HPC (49). We tested whether an incubation for 18 h with either IL-3, SCF, or G-CSF affected the chemotaxis of human BM CD34+ cells to SDF-1 (Fig. 5). IL-3 induced a significant increase (2.2 fold) in the percentage of cells responding to SDF-1. Incubation of CD34+ cells with SCF or G-CSF resulted in increased chemotaxis of these cells to SDF-1 (1.4- to 1.9-fold), but which did not reach statistical significance. A similar increase in chemotactic activity after exposure to IL-3 was observed using PB CD34+ cells (data not shown).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Blood Research, Inc., Boston, Massachusetts, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus