Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells |
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Authors: | Dar Ayelet Goichberg Polina Shinder Vera Kalinkovich Alexander Kollet Orit Netzer Neta Margalit Raanan Zsak Marion Nagler Arnon Hardan Izhar Resnick Igor Rot Antal Lapidot Tsvee |
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Affiliation: | Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. |
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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. |
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