Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells

Ayelet Dar; Polina Goichberg; Vera Shinder; Alexander Kalinkovich; Orit Kollet; Neta Netzer; Raanan Margalit; Marion Zsak; Arnon Nagler; Izhar Hardan; Igor Resnick; Antal Rot; Tsvee Lapidot

doi:10.1038/ni1251

Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells

Ayelet Dar, Polina Goichberg, Vera Shinder, Alexander Kalinkovich, Orit Kollet, Neta Netzer, Raanan Margalit, Marion Zsak, Arnon Nagler, Izhar Hardan, Igor Resnick, Antal Rot, Tsvee Lapidot

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1038-46
Number of pages	9
Journal	Nature immunology
Volume	6
Issue number	10
DOIs	https://doi.org/10.1038/ni1251
Publication status	Published - Oct 2005

Keywords

Animals
Antigens, CD34
Bone Marrow
Cell Movement
Cells, Cultured
Chemokine CXCL12
Chemokines, CXC
Endothelial Cells
Hematopoietic Stem Cells
Homeostasis
Humans
Immunity, Active
Mice
Mice, Inbred NOD
Mice, SCID
Receptors, CXCR4
Stromal Cells

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10.1038/ni1251

Cite this

Dar, A., Goichberg, P., Shinder, V., Kalinkovich, A., Kollet, O., Netzer, N., Margalit, R., Zsak, M., Nagler, A., Hardan, I., Resnick, I., Rot, A., & Lapidot, T. (2005). Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nature immunology, 6(10), 1038-46. https://doi.org/10.1038/ni1251

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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.",

keywords = "Animals, Antigens, CD34, Bone Marrow, Cell Movement, Cells, Cultured, Chemokine CXCL12, Chemokines, CXC, Endothelial Cells, Hematopoietic Stem Cells, Homeostasis, Humans, Immunity, Active, Mice, Mice, Inbred NOD, Mice, SCID, Receptors, CXCR4, Stromal Cells",

author = "Ayelet Dar and Polina Goichberg and Vera Shinder and Alexander Kalinkovich and Orit Kollet and Neta Netzer and Raanan Margalit and Marion Zsak and Arnon Nagler and Izhar Hardan and Igor Resnick and Antal Rot and Tsvee Lapidot",

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Dar, A, Goichberg, P, Shinder, V, Kalinkovich, A, Kollet, O, Netzer, N, Margalit, R, Zsak, M, Nagler, A, Hardan, I, Resnick, I, Rot, A & Lapidot, T 2005, 'Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells', Nature immunology, vol. 6, no. 10, pp. 1038-46. https://doi.org/10.1038/ni1251

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T1 - Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells

AU - Dar, Ayelet

AU - Goichberg, Polina

AU - Shinder, Vera

AU - Kalinkovich, Alexander

AU - Kollet, Orit

AU - Netzer, Neta

AU - Margalit, Raanan

AU - Zsak, Marion

AU - Nagler, Arnon

AU - Hardan, Izhar

AU - Resnick, Igor

AU - Rot, Antal

AU - Lapidot, Tsvee

PY - 2005/10

Y1 - 2005/10

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, CD34

KW - Bone Marrow

KW - Cell Movement

KW - Cells, Cultured

KW - Chemokine CXCL12

KW - Chemokines, CXC

KW - Endothelial Cells

KW - Hematopoietic Stem Cells

KW - Homeostasis

KW - Humans

KW - Immunity, Active

KW - Mice

KW - Mice, Inbred NOD

KW - Mice, SCID

KW - Receptors, CXCR4

KW - Stromal Cells

U2 - 10.1038/ni1251

DO - 10.1038/ni1251

M3 - Article

C2 - 16170318

SN - 1529-2908

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SP - 1038

EP - 1046

JO - Nature immunology

JF - Nature immunology

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