Expression of the G-CSF receptor on hematopoietic progenitor cells is not required for their mobilization by G-CSF.
The mechanisms that regulate hematopoietic progenitor cell (HPC) mobilization from the bone marrow to blood have not yet been defined. HPC mobilization by granulocyte colony-stimulating factor (G-CSF), cyclophosphamide (CY), or interleukin-8 but not flt-3 ligand is markedly impaired in G-CSF receptor-deficient (G-CSFR-deficient) mice. G-CSFR is expressed on mature hematopoietic cells, HPCs, and stromal cells, which suggests that G-CSFR signals in one or more of these cell types was required for mobilization by these agents. To define the cell type(s) responsible for G-CSF-dependent mobilization, a series of chimeric mice were generated using bone marrow transplantation. Mobilization studies in these chimeras demonstrated that expression of the G-CSFR on transplantable hematopoietic cells but not stromal cells is required for CY- or G-CSF-induced mobilization. Moreover, in irradiated mice reconstituted with both wild type and G-CSFR-deficient bone marrow cells, treatment with CY or G-CSF resulted in the equal mobilization of both types of HPCs. This result held true for a broad spectrum of HPCs including colony-forming cells, CD34(+) lineage(-) and Sca(+) lineage(-) cells, and long-term culture initiating cells. Collectively, these data provide the first definitive evidence that expression of the G-CSFR on HPCs is not required for their mobilization by G-CSF and suggest a model in which G-CSFR-dependent signals act in trans to mobilize HPCs from the bone marrow.
Liu
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Washington University School of Medicine, Division of Bone Marrow Transplantation and Stem Cell Biology, Department of Internal Medicine, St. Louis, MO 63110-1093, USA.
Poursine-Laurent
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D000818:Animals; D016026:Bone Marrow Transplantation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000502:physiology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology*; D051379:Mice; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D018183:Transplantation Chimera
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor