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 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.
Aiuti
A
A
Center for Blood Research, Inc., Boston, Massachusetts, USA.
Webb
I J
IJ
Bleul
C
C
Springer
T
T
Gutierrez-Ramos
J C
JC
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054407:Chemokine CCL4; D054377:Chemokine CXCL12; D018925:Chemokines / Q000302:isolation & purification / Q000494:pharmacology*; D019743:Chemokines, CXC; D002633:Chemotaxis / Q000187:drug effects*; D017077:Culture Media, Conditioned; D005260:Female; D005312:Fetal Blood; D006684:HLA-DR Antigens; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000276:immunology / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases; D011247:Pregnancy; D017154:Stromal Cells
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; C515255:CXCL12 protein, human; D054407:Chemokine CCL4; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D006684:HLA-DR Antigens; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium