| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Liver Research Group,* Institute of Biomedical Research, MRC Centre for Immune Regulation, The University of Birmingham Medical School, Edgbaston, Birmingham, United Kingdom; and Pfizer Global Research and Development, Groton, Connecticut
T cells infiltrating the inflamed liver express high levels of CXCR3 and show enhanced migration to CXCR3 ligands in chemotactic assays. Moreover, CXCR3 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 CXCR3 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 CXCR3high lymphocytes, we isolated T cells from human liver tissue and studied their behavior in flow-based adhesion assays. We demonstrate that CXCR3 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 CXCR3 ligands secreted by the endothelium or by exogenous CXCR3 ligands derived from other cell types and presented by the endothelium. This study thus demonstrates that activation of CXCR3 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.
This article has been cited by other articles:
 |
|
 |
|
  M. Heydtmann Macrophages in Hepatitis B and Hepatitis C Virus Infections J. Virol., April 1, 2009; 83(7): 2796 - 2802. [Full Text] [PDF]
|
|
|
|
 |
|
 D H Adams, B Eksteen, and S M Curbishley Immunology of the gut and liver: a love/hate relationship Gut, June 1, 2008; 57(6): 838 - 848. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Miles, E. Liaskou, B. Eksteen, P. F. Lalor, and D. H. Adams CCL25 and CCL28 promote {alpha}4{beta}7-integrin-dependent adhesion of lymphocytes to MAdCAM-1 under shear flow Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1257 - G1267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Hokeness, E. S. Deweerd, M. W. Munks, C. A. Lewis, R. P. Gladue, and T. P. Salazar-Mather CXCR3-Dependent Recruitment of Antigen-Specific T Lymphocytes to the Liver during Murine Cytomegalovirus Infection J. Virol., February 1, 2007; 81(3): 1241 - 1250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Eksteen, A. Miles, S. M. Curbishley, C. Tselepis, A. J. Grant, L. S. K. Walker, and D. H. Adams Epithelial Inflammation Is Associated with CCL28 Production and the Recruitment of Regulatory T Cells Expressing CCR10 J. Immunol., July 1, 2006; 177(1): 593 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Heydtmann, D. Hardie, P. L. Shields, J. Faint, C. D. Buckley, J. J. Campbell, M. Salmon, and D. H. Adams Detailed Analysis of Intrahepatic CD8 T Cells in the Normal and Hepatitis C-Infected Liver Reveals Differences in Specific Populations of Memory Cells with Distinct Homing Phenotypes J. Immunol., July 1, 2006; 177(1): 729 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Duftner, C Dejaco, W Kullich, A Klauser, C Goldberger, A Falkenbach, and M Schirmer Preferential type 1 chemokine receptors and cytokine production of CD28- T cells in ankylosing spondylitis Ann Rheum Dis, May 1, 2006; 65(5): 647 - 653. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
