title: Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells.
abstract: Regulation of the availability of chemokine SDF-1 (CXCL12) in bone marrow is still not fully understood. Here we describe a unique function for the chemokine receptor CXCR4 expressed on bone marrow endothelial cells, which efficiently internalize circulating SDF-1, resulting in its translocation into the bone marrow. Translocated SDF-1 increased the homing of transplanted human CD34(+) hematopoietic progenitors to the bone marrow. The chemokine transporter function of CXCR4 was a characteristic of endothelial and stromal cells but not of hematopoietic cells. Thus, chemokine translocation across the blood-bone marrow barrier allows effective transfer of functional SDF-1 from the periphery to the stem cell niche in the bone marrow during both homeostasis and 'alarm' situations.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Dar
authors.forename: Polina
authors.initials: P
authors.lastname: Goichberg
authors.forename: Vera
authors.initials: V
authors.lastname: Shinder
authors.forename: Alexander
authors.initials: A
authors.lastname: Kalinkovich
authors.forename: Orit
authors.initials: O
authors.lastname: Kollet
authors.forename: Neta
authors.initials: N
authors.lastname: Netzer
authors.forename: Raanan
authors.initials: R
authors.lastname: Margalit
authors.forename: Marion
authors.initials: M
authors.lastname: Zsak
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Izhar
authors.initials: I
authors.lastname: Hardan
authors.forename: Igor
authors.initials: I
authors.lastname: Resnick
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
authors.forename: Tsvee
authors.initials: T
authors.lastname: Lapidot
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D001853:Bone Marrow / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D042783:Endothelial Cells / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007110:Immunity, Active / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019718:Receptors, CXCR4 / Q000502:physiology*; D017154:Stromal Cells / Q000276:immunology*
chemical_list: D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4