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HPB Surgery
Volume 2012, Article ID 480893, 10 pages
http://dx.doi.org/10.1155/2012/480893
Research Article

ICAM-1 Upregulation in Ethanol-Induced Fatty Murine Livers Promotes Injury and Sinusoidal Leukocyte Adherence after Transplantation

1Center for Cell Death, Injury & Regeneration, Department of Pharmaceutical & Biomedical Sciences, Medical University of South Carolina, 280 Calhoun Street, MSC 140, Charleston, SC 29425, USA
2Department of Surgery, Medical University of South Carolina, 280 Calhoun Street, MSC 140, Charleston, SC 29425, USA
3Department of Cell & Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA
4Department of Medicine, University of Regensburg, 93053 Regensburg, Germany
5Department of Biochemistry & Molecular Biology, Medical University of South Carolina, 280 Calhoun Street, MSC 140, Charleston, SC 29425, USA

Received 30 January 2012; Accepted 30 April 2012

Academic Editor: Peter Schemmer

Copyright © 2012 Tom P. Theruvath et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Transplantation of ethanol-induced steatotic livers causes increased graft injury. We hypothesized that upregulation of hepatic ICAM-1 after ethanol produces increased leukocyte adherence, resulting in increased generation of reactive oxygen species (ROS) and injury after liver transplantation (LT). Methods. C57BL/6 wildtype (WT) and ICAM-1 knockout (KO) mice were gavaged with ethanol (6 g/kg) or water. LT was then performed into WT recipients. Necrosis and apoptosis, 4-hydroxynonenal (4-HNE) immunostaining, and sinusoidal leukocyte movement by intravital microscopy were assessed. Results. Ethanol gavage of WT mice increased hepatic triglycerides 10-fold compared to water treatment (P<0.05). ICAM-1 also increased, but ALT was normal. At 8 h after LT of WT grafts, ALT increased 2-fold more with ethanol than water treatment (P<0.05). Compared to ethanol-treated WT grafts, ALT from ethanol-treated KO grafts was 78% less (P<0.05). Apoptosis also decreased by 75% (P<0.05), and 4-HNE staining after LT was also decreased in ethanol-treated KO grafts compared to WT. Intravital microscopy demonstrated a 2-fold decrease in leukocyte adhesion in KO grafts compared to WT grafts. Conclusions. Increased ICAM-1 expression in ethanol-treated fatty livers predisposes to leukocyte adherence after LT, which leads to a disturbed microcirculation, oxidative stress and graft injury.