Nature Immunology
6, 1038 - 1046 (2005)
Published online: 18 September 2005; | doi:10.1038/ni1251
Chemokine receptor CXCR4−dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cellsAyelet Dar1, Polina Goichberg1, Vera Shinder2, Alexander Kalinkovich1, Orit Kollet1, Neta Netzer1, Raanan Margalit1, Marion Zsak3, Arnon Nagler4, Izhar Hardan4, Igor Resnick5, Antal Rot3
& Tsvee Lapidot11
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. 2
Unit of Electron Microscopy, Weizmann Institute of Science, Rehovot 76100, Israel. 3
Novartis Institutes for BioMedical Research, Vienna A1230, Austria. 4
Bone Marrow Transplantation Department, Chaim Sheba Medical Center, Tel Hashomer 52662, Israel. 5
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Jerusalem 91120, Israel.
Correspondence should be addressed to Tsvee Lapidot tsvee.lapidot@weizmann.ac.il 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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