Stromal cell-derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G(0)/G(1) transition in CD34(+) cells: evidence for an autocrine/paracrine mechanism.
The stromal cell-derived factor 1 (SDF-1) chemokine has various effects on hematopoietic cell functions. Its role in migration and homing of hematopoietic progenitors is currently well established. Previously it was shown that SDF-1 stimulates myeloid progenitor proliferation in synergy with cytokines. Results of this study indicate that SDF-1 alone promotes survival of purified CD34(+) cells from human unmobilized peripheral blood (PB) by counteracting apoptosis as demonstrated by its capacity to reduce DNA fragmentation, annexin-V(+) cell number, and APO2.7 detection and to modulate bcl-2 homolog protein expression. The study demonstrates that SDF-1, produced by sorted CD34(+)CD38(+) cells and over-released in response to cell damage, exerts an antiapoptotic effect on CD34(+) cells through an autocrine/paracrine regulatory loop. SDF-1 participates in the autonomous survival of circulating CD34(+) cells and its effect required activation of the phosphotidyl inositol 3 kinase (PI3-K)/Akt axis. Cell sorting based on Hoechst/pyroninY fluorescences shows that SDF-1 production is restricted to cycling CD34(+) cells. SDF-1 triggers G(0) quiescent cells in G(1) phase and, in synergy with thrombopoietin or Steel factor, makes CD34(+) cells progress through S+G(2)/M phases of cell cycle. By assessing sorted CD34(+)CD38(-) and CD34(+)CD38(+) in semisolid culture, the study demonstrates that SDF-1 promotes survival of clonogenic progenitors. In conclusion, the results are the first to indicate a role for endogenous SDF-1 in primitive hematopoiesis regulation as a survival and cell cycle priming factor for circulating CD34(+) cells. The proposal is made that SDF-1 may contribute to hematopoiesis homeostasis by participating in the autonomous survival and cycling of progenitors under physiologic conditions and by protecting them from cell aggression in stress situations.
Lataillade
Jean-Jacques
JJ
Laboratoire d'Immunologie Cellulaire, Centre de Transfusion Sanguine des Armées Jean Julliard, Clamart Cedex, France.
Clay
Denis
D
Bourin
Philippe
P
Hérodin
Françis
F
Dupuy
Catherine
C
Jasmin
Claude
C
Le Bousse-Kerdilès
Marie-Caroline
MC
D018952:Antigens, CD34 / Q000097:blood*; D017209:Apoptosis / Q000187:drug effects*; D019898:Autocrine Communication; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology* / Q000502:physiology; D016193:G1 Phase / Q000502:physiology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007399:Interphase / Q000187:drug effects*; D019899:Paracrine Communication; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D019718:Receptors, CXCR4 / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000502:physiology
D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; D019869:Phosphatidylinositol 3-Kinases