The granulocyte colony-stimulating factor receptor is required for the mobilization of murine hematopoietic progenitors into peripheral blood by cyclophosphamide or interleukin-8 but not flt-3 ligand.
Hematopoietic progenitor cells (HPC) can be mobilized from the bone marrow into the peripheral circulation in response to a number of stimuli including hematopoietic growth factors, cytotoxic agents, and certain chemokines. Despite significant differences in their biological activities, these stimuli result in the mobilization of HPC with a similar phenotype, suggesting that a common mechanism for mobilization may exist. In this study, the role of granulocyte colony-stimulating factor (G-CSF) in progenitor mobilization was examined using G-CSF receptor (G-CSFR)-deficient mice. In contrast to wild-type mice, no increase in circulating colony-forming cells (CFU-C), CD34+ lineage- progenitors, or day 12 colony-forming unit-spleen progenitors (CFU-S) was detected in G-CSFR-deficient mice after cyclophosphamide administration. This defect was not due to a failure to regenerate HPC following cyclophosphamide administration as the number of CFU-C in the bone marrow of G-CSFR-deficient mice was increased relative to wild-type mice. Likewise, no increase in circulating CFU-C was detected in G-CSFR-deficient mice following interleukin-8 (IL-8) administration. In contrast, mobilization of HPC in response to flt-3 ligand was nearly normal. These results show that the G-CSFR is required for mobilization in response to cyclophosphamide or IL-8 but not flt-3 ligand and suggest that the G-CSFR may play an important and previously unexpected role in HPC migration.
Liu
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Department of Medicine, Washington University Medical School, St Louis, MO 63110-1093, USA.
Poursine-Laurent
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D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D016209:Interleukin-8 / Q000494:pharmacology*; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology
D016209:Interleukin-8; D008565:Membrane Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide