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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ADP-ribosyl Cyclase
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ADP-ribosyl Cyclase 1
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Antigens, CD*
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Antigens, CD34*
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Antigens, Differentiation
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Bone Marrow / pathology
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Bone Marrow Cells
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Breast Neoplasms / blood
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Breast Neoplasms / immunology
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Breast Neoplasms / pathology
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Calcium / metabolism
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Cells, Cultured
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Chemokine CCL4
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Chemokine CXCL12
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Chemokines / isolation & purification
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Chemokines / pharmacology*
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Chemokines, CXC*
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Chemotaxis / drug effects*
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Culture Media, Conditioned
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Female
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Fetal Blood
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HLA-DR Antigens
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / physiology*
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Humans
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Lymphoma, Non-Hodgkin / blood
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Lymphoma, Non-Hodgkin / immunology
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Lymphoma, Non-Hodgkin / pathology
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Macrophage Inflammatory Proteins / pharmacology
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Membrane Glycoproteins
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N-Glycosyl Hydrolases
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Pregnancy
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Stromal Cells
Substances
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Antigens, CD
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Antigens, CD34
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Antigens, Differentiation
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CXCL12 protein, human
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Chemokine CCL4
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Chemokine CXCL12
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Chemokines
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Chemokines, CXC
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Culture Media, Conditioned
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HLA-DR Antigens
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Macrophage Inflammatory Proteins
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Membrane Glycoproteins
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N-Glycosyl Hydrolases
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ADP-ribosyl Cyclase
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CD38 protein, human
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ADP-ribosyl Cyclase 1
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Calcium