Background/Aims
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.
Methods
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).
Results
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.
Conclusions
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.
Abbreviations:
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)Keywords
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Article info
Publication history
Published online: February 09, 2009
Accepted:
November 1,
2008
Received in revised form:
October 17,
2008
Received:
June 4,
2008
Associate Editor: V. BarnabaFootnotes
☆The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.
Identification
Copyright
© 2009 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
