title: G-CSF is an essential regulator of neutrophil trafficking from the bone marrow to the blood.
abstract: Neutrophils are released from the bone marrow in a regulated fashion to maintain homeostatic levels in the blood and to respond to physiological stresses, including infection. We show that under basal conditions granulocyte colony-stimulating factor (G-CSF) is an essential regulator of neutrophil release from the bone marrow. Nonredundant signals generated by the membrane-proximal 87 amino acids of the G-CSF receptor (G-CSFR) are sufficient to mediate this response. Surprisingly, G-CSFR expression on neutrophils is neither necessary nor sufficient for their mobilization from the bone marrow, suggesting that G-CSF induces neutrophil mobilization indirectly through the generation of trans-acting signals. Evidence is provided suggesting that downregulation of stromal cell-derived factor 1 expression in the bone marrow may represent such a signal.
authors.affiliation: Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Semerad
authors.forename: Fulu
authors.initials: F
authors.lastname: Liu
authors.forename: Alyssa D
authors.initials: AD
authors.lastname: Gregory
authors.forename: Katherine
authors.initials: K
authors.lastname: Stumpf
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Link
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000502:physiology; D001854:Bone Marrow Cells / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D016209:Interleukin-8 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016296:Mutagenesis; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016209:Interleukin-8; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor