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

A Dar, P Goichberg, V Shinder, A Kalinkovich… - Nature …, 2005 - nature.com
A Dar, P Goichberg, V Shinder, A Kalinkovich, O Kollet, N Netzer, R Margalit, M Zsak…
Nature immunology, 2005nature.com
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 …
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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