Research Article| Volume 50, ISSUE 4, P755-765, April 2009

Leukocyte transmigration in inflamed liver: A role for endothelial cell-selective adhesion molecule

Published:February 09, 2009DOI:


      This study was designed to investigate the role of endothelial cell-selective adhesion molecule (ESAM), a recently discovered receptor expressed in endothelial tight junctions and platelets, for leukocyte migration in inflamed liver.


      The role of ESAM for leukocyte migration in the liver was analyzed using ESAM-deficient mice in a model of warm hepatic ischemia-reperfusion (90 min/30–360 min).


      As shown by immunostaining, ESAM is expressed in sinusoids as well as in venules and is not upregulated upon I/R. Emigrated leukocytes were quantified in tissue sections. Postischemic neutrophil transmigration was significantly attenuated in ESAM−/− mice after 2 h of reperfusion, whereas it was completely restored after 6 h. In contrast, T-cell migration did not differ between ESAM+/+ and ESAM−/− mice. Using intravital microscopy, we demonstrate that ESAM deficiency attenuates I/R-induced vascular leakage after 30 min of reperfusion. The I/R-induced elevation in AST/ALT activity, the sinusoidal perfusion failure, and the number of TUNEL-positive hepatocytes were comparable between ESAM+/+ and ESAM−/− mice.


      ESAM is expressed in the postischemic liver and mediates neutrophil but not T-cell transmigration during early reperfusion. ESAM deficiency attenuates I/R-induced vascular leakage and does not affect leukocyte adherence. Despite the effect on neutrophil migration, ESAM-deficiency does not protect from I/R-induced injury.


      ESAM (endothelial cell-selective adhesion molecule), FITC (Fluorescein isothiocyanate), HPF (high-power fields), I/R (ischemia-reperfusion), JAM (junctional adhesion molecule), PECAM-1 (platelet endothelial cell adhesion molecule-1), ROS (reactive oxygen species), TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling)


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