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 . 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 . Compared to ethanol-treated WT grafts, ALT from ethanol-treated KO grafts was 78% less . Apoptosis also decreased by 75% , 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. 1. Introduction After cold ischemic liver storage for transplantation, reperfusion injury may lead to poor initial graft function and even graft failure. This injury is more severe and causes increased morbidity and mortality when steatotic donor livers are used [1, 2]. Because of the increasing incidence of nonalcoholic steatohepatitis in the general population and the association of vehicular accidents with steatosis-causing alcohol use and abuse, an important fraction of potential human donor livers is steatotic. Such marginal steatotic livers are increasingly used as liver grafts because of the liver donor shortage and the expanding waiting list for liver transplantation. Sinusoidal endothelial cells and hepatocytes are particularly susceptible to ischemia/reperfusion (I/R) injury and consequent apoptotic and necrotic cell death, as shown by both in vitro and in vivo studies [3–6]. After liver I/R, recruitment of neutrophils and other inflammatory cells aggravates injury [7, 8]. Neutrophil recruitment also contributes to liver injury after endotoxin, sepsis, and chronic ethanol treatment [9–12]. Hepatic infiltration with neutrophils results in production of reactive oxygen species (ROS) and oxidative stress,
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