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

Abstract EN

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.