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

Nat Immunol. 2005 Oct;6(10):1038-46. doi: 10.1038/ni1251. Epub 2005 Sep 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Antigens, CD34
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Receptors, CXCR4