Stromal-derived factor-1 and its receptor, CXCR4, are constitutively expressed by mouse liver sinusoidal endothelial cells: implications for the regulation of hematopoietic cell migration to the liver during extramedullary hematopoiesis

Stem Cells Dev. 2012 Aug 10;21(12):2142-51. doi: 10.1089/scd.2011.0565. Epub 2012 Jan 26.

Abstract

Stromal-derived factor (SDF)-1 is the main regulating factor for trafficking/homing of hematopoietic stem cells (HSC) to the bone marrow (BM). It is possible that this chemokine may also play a fundamental role in regulating the migration of HSC to several organs during extramedullary hematopoiesis. Because liver sinusoidal endothelial cells (LSEC) constitute an extramedullary niche for HSC, it is possible that these cells represent one of the main cellular sources of SDF-1 at the liver. Here, we show that LSEC express SDF-1 at the mRNA and protein level. Biological assays showed that conditioned medium from LSEC (LSEC-CM) stimulated the migration of BM progenitor lineage-negative (BM/Lin⁻) cells. This effect was significantly reduced by AMD3100, indicating that the SDF-1/CXCR4 axis is involved in the stimulatory migrating effect induced by LSEC-CM. Early localization of HSC in SDF-1-expressing LSEC microenvironment together with increased levels of this chemokine in hepatic homogenates was found in an experimental model of liver extramedullary hematopoiesis. Flow cytometry studies showed that LSEC express the CXCR4 receptor. Functional assays showed that activation of this receptor by SDF-1 stimulated the migration of LSEC and increased the expression of PECAM-1. Our findings suggest that LSEC through the production of SDF-1 may constitute a fundamental niche for regulation of HSC migration to the liver. To our knowledge, this is the first report showing that LSEC not only express and secrete SDF-1, but also its receptor CXCR4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Movement
  • Cells, Cultured
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism*
  • Culture Media, Conditioned
  • Endothelial Cells / metabolism*
  • Female
  • Gene Expression
  • Hematopoiesis, Extramedullary*
  • Hematopoietic Stem Cells / physiology*
  • Interleukin-6 / physiology
  • Liver / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • Tumor Necrosis Factor-alpha / physiology
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Culture Media, Conditioned
  • Cxcl12 protein, mouse
  • Interleukin-6
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, CXCR4
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1