Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells.
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.
Dar
Ayelet
A
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Goichberg
Polina
P
Shinder
Vera
V
Kalinkovich
Alexander
A
Kollet
Orit
O
Netzer
Neta
N
Margalit
Raanan
R
Zsak
Marion
M
Nagler
Arnon
A
Hardan
Izhar
I
Resnick
Igor
I
Rot
Antal
A
Lapidot
Tsvee
T
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*
D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4