Focal liver necrosis appears early after partial hepatectomy and is dependent on T cells and antigen delivery from the gut.

Abstract

INTRODUCTION:

Progressive liver failure may develop following removal of a large part of the liver or transplantation of a small for size liver graft. The pathophysiology of this clinical syndrome is only partially understood.

METHODS:

We assessed liver damage and hepatocyte 5-bromo-2'-deoxyuridine (BrdU) incorporation following partial hepatectomy (PH) in C57BL/6, BALB/C and immune-deficient mice. Hepatic lymphocyte subpopulations were characterized. Lipopolysaccharide (LPS) treatment and bowel decontamination determined the role of gut antigens.

RESULTS:

Discrete, round necrotic lesions were observed as early as 2 h following 70%, but not 30% PH. In immune competent mice the extent of hepatocyte necrosis inversely correlated with BrdU incorporation. T, natural killer and natural killer T cells were recruited to the liver early after PH; however, only T-cell depletion abrogated hepatic necrosis. Hepatic injury was significantly reduced in non-obese diabetic/severe combined immunodeficient mice undergoing PH, while BrdU incorporation was not affected. Liver injury was augmented by LPS injection and reduced by gut decontamination.

CONCLUSIONS:

A distinct pattern of early focal hepatic necrosis is observed following extensive PH in mice. T cells infiltrating the liver immediately after PH and gut-derived antigens are indispensable for the observed liver necrosis and may thus provide therapeutic targets to ameliorate liver damage following PH.

• Authors: Noam Rudich, Gideon Zamir, Orit Pappo, Zipora Shlomai, Muhamad Faroja, Ido D Weiss, Hanna Wald, Eithan Galun, Amnon Peled, Ori Wald
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 29 Issue 8 Pg. 1273-84 (Sep 2009) ISSN: 1478-3231 [Electronic] United States
• PMID: 19538448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Antibodies, Blocking
• Antigens, Bacterial
• Lipopolysaccharides
• Bromodeoxyuridine

Topics

• Adoptive Transfer
• Animals
• Anti-Bacterial Agents (pharmacology)
• Antibodies, Blocking (pharmacology)
• Antigen Presentation
• Antigens, Bacterial (immunology)
• Bone Marrow Transplantation
• Bromodeoxyuridine (metabolism)
• Cell Proliferation
• Disease Models, Animal
• Gastric Mucosa (immunology)
• Hepatectomy (adverse effects)
• Intestines (drug effects, immunology, microbiology)
• Lipopolysaccharides (pharmacology)
• Liver (immunology, metabolism, pathology)
• Liver Cirrhosis (etiology, immunology, pathology)
• Liver Regeneration (physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Nude
• Mice, SCID
• Specific Pathogen-Free Organisms
• T-Lymphocytes (immunology)