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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We thank B. Frisch and B. Lifschitz–Mercer (Sourasky Medical Center, Tel-Aviv, Israel) for providing human bone marrow specimens; and A. Globerson, D. Zipori, R. Alon and S. Berrih-Aknin for critical remarks and discussions. Supported by The Israel Science Foundation (794/04) and Ares-Serono Group and by the Edith Stein Professional Chair of Immunology (T.L.).
The authors declare no competing financial interests.
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Dar, A., Goichberg, P., Shinder, V. et al. Chemokine receptor CXCR4–dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nat Immunol 6, 1038–1046 (2005). https://doi.org/10.1038/ni1251
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