title: G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4.
abstract: Granulocyte colony-stimulating factor (G-CSF) induced hematopoietic stem cell mobilization is widely used for clinical transplantation; however, the mechanism is poorly understood. We report here that G-CSF induced a reduction of the chemokine stromal cell derived factor 1 (SDF-1) and an increase in its receptor CXCR4 in the bone marrow (BM), whereas their protein expression in the blood was less affected. The gradual decrease of BM SDF-1, due mostly to its degradation by neutrophil elastase, correlated with stem cell mobilization. Elastase inhibition reduced both activities. Human and murine stem cell mobilization was inhibited by neutralizing CXCR4 or SDF-1 antibodies, demonstrating SDF-1 CXCR4 signaling in cell egress. We suggest that manipulation of SDF-1 CXCR4 interactions may be a means with which to control the navigation of progenitors between the BM and blood to improve the outcome of clinical stem cell transplantation.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Petit
authors.forename: Martine
authors.initials: M
authors.lastname: Szyper-Kravitz
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Meir
authors.initials: M
authors.lastname: Lahav
authors.forename: Amnon
authors.initials: A
authors.lastname: Peled
authors.forename: Liliana
authors.initials: L
authors.lastname: Habler
authors.forename: Tanya
authors.initials: T
authors.lastname: Ponomaryov
authors.forename: Russell S
authors.initials: RS
authors.lastname: Taichman
authors.forename: Fernando
authors.initials: F
authors.lastname: Arenzana-Seisdedos
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Judith
authors.initials: J
authors.lastname: Sandbank
authors.forename: Dov
authors.initials: D
authors.lastname: Zipori
authors.forename: Tsvee
authors.initials: T
authors.lastname: Lapidot
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008223:Lymphoma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; D010196:Pancreatic Elastase