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

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 transplan...

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Autores principales: Theruvath, Tom P., Ramshesh, Venkat K., Zhong, Zhi, Currin, Robert T., Karrasch, Thomas, Lemasters, John J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385666/
https://www.ncbi.nlm.nih.gov/pubmed/22778492
http://dx.doi.org/10.1155/2012/480893
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author Theruvath, Tom P.
Ramshesh, Venkat K.
Zhong, Zhi
Currin, Robert T.
Karrasch, Thomas
Lemasters, John J.
author_facet Theruvath, Tom P.
Ramshesh, Venkat K.
Zhong, Zhi
Currin, Robert T.
Karrasch, Thomas
Lemasters, John J.
author_sort Theruvath, Tom P.
collection PubMed
description 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.
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spelling pubmed-33856662012-07-09 ICAM-1 Upregulation in Ethanol-Induced Fatty Murine Livers Promotes Injury and Sinusoidal Leukocyte Adherence after Transplantation Theruvath, Tom P. Ramshesh, Venkat K. Zhong, Zhi Currin, Robert T. Karrasch, Thomas Lemasters, John J. HPB Surg Research Article 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. Hindawi Publishing Corporation 2012 2012-06-18 /pmc/articles/PMC3385666/ /pubmed/22778492 http://dx.doi.org/10.1155/2012/480893 Text en Copyright © 2012 Tom P. Theruvath et al. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Research Article
Theruvath, Tom P.
Ramshesh, Venkat K.
Zhong, Zhi
Currin, Robert T.
Karrasch, Thomas
Lemasters, John J.
ICAM-1 Upregulation in Ethanol-Induced Fatty Murine Livers Promotes Injury and Sinusoidal Leukocyte Adherence after Transplantation
title ICAM-1 Upregulation in Ethanol-Induced Fatty Murine Livers Promotes Injury and Sinusoidal Leukocyte Adherence after Transplantation
title_full ICAM-1 Upregulation in Ethanol-Induced Fatty Murine Livers Promotes Injury and Sinusoidal Leukocyte Adherence after Transplantation
title_fullStr ICAM-1 Upregulation in Ethanol-Induced Fatty Murine Livers Promotes Injury and Sinusoidal Leukocyte Adherence after Transplantation
title_full_unstemmed ICAM-1 Upregulation in Ethanol-Induced Fatty Murine Livers Promotes Injury and Sinusoidal Leukocyte Adherence after Transplantation
title_short ICAM-1 Upregulation in Ethanol-Induced Fatty Murine Livers Promotes Injury and Sinusoidal Leukocyte Adherence after Transplantation
title_sort icam-1 upregulation in ethanol-induced fatty murine livers promotes injury and sinusoidal leukocyte adherence after transplantation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385666/
https://www.ncbi.nlm.nih.gov/pubmed/22778492
http://dx.doi.org/10.1155/2012/480893
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