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

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. Postischermic 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. (c) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.