Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatic expression of major histocompatibility complex (MHC) antigens is normally limited. However aberrant expression may occur in cholestatic diseases or following liver transplantation. The aim of this work was to investigate the effect of normothermic ischemia on hepatocellular MHC expression. Temporary (90-min) normothermic ischemia of the liver was induced in inbred rats. There was a significant elevation of aspartate aminotransferase and alanine aminotransferase levels after ischemia, rising to their maximum by 6 h. Histologic findings showed large, confluent areas of necrosis, and preserved areas were seen with centrolobular congestion and macrovacuolar steatosis. Expression of MHC class I and II antigens was detected using the immunoperoxidase technique, 1 h, 12 h, 3 days, 7 days and 1 month after the end of intervention. A marked induction of the expression of class I, but not of class II, MHC antigens was observed on the hepatocyte membranes after ischemia. We suggest that normothermic ischemia can occur postoperatively in human liver transplantation and may cause increased expression of class I MHC antigens on hepatocytes, leading to increased sensitivity of liver allografts to rejection by cytotoxic T cells.
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PMID:Normothermic ischemia induces major histocompatibility complex class I expression in hepatocytes. 881 49

Hepatocytes constitute the principal site of listerial replication in the livers of mice infected i.v. CD8+ T lymphocytes play a predominant role in the host defenses to Listeria monocytogenes. In vitro experiments by others undertaken to delineate the functions of CD8+ T lymphocytes have focused primarily on their interaction with Listeria-infected macrophages. Such experiments do not address directly the role of CD8+ T lymphocytes in eliminating the bulk of Listeria replicating within the liver. Here, we report that immune CD8+ T cells at an E:T cell ratio > or = 10:1 lysed Listeria-infected hepatocytes as judged by the following two criteria. Aspartate aminotransferase activity in the culture supernatants, indicative of hepatocyte damage, increased significantly. Conversely, infected hepatocytes cocultured with immune CD8+ T cells exhibited a marked reduction in viable intracellular Listeria assessed by CFUs. Neither immune CD4+ T cells nor nonimmune CD8+ T cells caused a similar increase in aspartate aminotransferase activity released or a decrease in intracellular bacteria. Immune CD8+ T cell-mediated lysis of infected hepatocytes was restricted by classical MHC class I (H-2Kb) molecules and was inhibited by the presence of either brefeldin A or mAb specific for CD8. These results suggest that the predominant role of CD8+ T lymphocytes in host resistance to listerial infections of the liver may be due to their capacity to lyse infected hepatocytes.
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PMID:Immune CD8+ T lymphocytes lyse Listeria monocytogenes-infected hepatocytes by a classical MHC class I-restricted mechanism. 897 1

Ag stimulation of CD8+ lymphocytes in vivo results in their migration to various tissues as well as the activation of a cytolytic program involving perforin, TNF-alpha, and Fas ligand. The liver is one of the main sites for infiltration by activated CD8+ T cells, and this is followed by the death of hepatocytes. The contribution of the various cytolytic components to this process is unclear. Hepatocyte damage by CD8+ T cells was studied using the MHC class I-restricted OVA-specific TCR transgenic mouse (OT-1) to examine the contribution of Fas to hepatocyte death. Activated CD8+ T cells from both OT-1 and Fas-deficient OT-1lpr mice migrated to the liver in similar numbers after OVA administration, but only in OT-1 mice was there evidence of significant hepatocyte damage histologically and by elevation of serum aspartate transaminase. These differences were not the result of inefficient induction of cytolytic activity in OT-1lpr liver T cells, since they were as cytolytic in vitro as OT-1 liver T cells. This was supported by findings of similar high levels of message for perforin, TNF-alpha, and Fas ligand in liver lymphocytes from both mice. These findings demonstrate that following Ag activation, infiltrating liver CD8+ T lymphocytes induce hepatocyte damage in a Fas-dependent manner.
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PMID:Liver damage by infiltrating CD8+ T cells is Fas dependent. 1171 37