CXCR 3 activation promotes lymphocyte transendothelial migration across human hepatic endothelium under fluid flow

Am J Pathol. 2005 Sep;167(3):887-99. doi: 10.1016/S0002-9440(10)62060-3.


T cells infiltrating the inflamed liver express high levels of CXCR 3 and show enhanced migration to CXCR 3 ligands in chemotactic assays. Moreover, CXCR 3 ligands are up-regulated on hepatic endothelium at sites of T-cell infiltration in chronic hepatitis, and their presence correlates with outcome of inflammatory liver disease. We used a flow-based adhesion assay with human hepatic endothelium to investigate the function of CXCR 3 on lymphocyte adhesion to and transmigration through hepatic endothelium under physiological conditions of blood flow. To more accurately model the function of in vivo activated CXCR 3(high) lymphocytes, we isolated T cells from human liver tissue and studied their behavior in flow-based adhesion assays. We demonstrate that CXCR 3 not only promoted the adhesion of effector T cells to endothelium from flow but also drove transendothelial migration. Moreover, these responses could be stimulated either by endogenous CXCR 3 ligands secreted by the endothelium or by exogenous CXCR 3 ligands derived from other cell types and presented by the endothelium. This study thus demonstrates that activation of CXCR 3 promotes lymphocyte adhesion and transendothelial migration under flow and that human hepatic endothelium can present functionally active chemokines secreted by other cell types within the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biliary Tract / metabolism
  • Biliary Tract / physiology
  • Blood Physiological Phenomena*
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / metabolism
  • Cell Movement / physiology*
  • Cells, Cultured
  • Chemokines / metabolism
  • Chemokines, CXC / metabolism
  • Cytokines / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology
  • Endothelium / physiology
  • Humans
  • Ligands
  • Liver / drug effects
  • Liver / metabolism
  • Liver / physiology*
  • Lymphocytes / metabolism
  • Lymphocytes / physiology*
  • Receptors, CXCR3
  • Receptors, Chemokine / metabolism
  • Receptors, Chemokine / physiology*
  • Tumor Necrosis Factor-alpha / pharmacology


  • CXCR3 protein, human
  • Cell Adhesion Molecules
  • Chemokines
  • Chemokines, CXC
  • Cytokines
  • Ligands
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha