Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After intraperitoneal infection with mouse hepatitis virus, strain JHM (JHMV), JHMV replicated in the spleen of C57BL/6 mice for a few days but cleared within a week. The acute viral clearance coincided with moderate expansion of CD8+T cells and modest expansion of CD4+T cells, and was impaired moderately in mice depleted of CD8+T cells and completely in mice depleted of both CD4+ and CD8+T cell subsets. Flow cytometric analysis showed that expression of cell surface markers on the spleen T cells changed during JHMV infection. CD8+T cells expressing increased amounts of CD11a, CD43, CD44 and CD49d, and those expressing decreased levels of T cell receptor alpha beta, CD8, CD45RB and L-selectin were expanded in the spleen after JHMV infection. However, they did not express CD11b, CD25 or NK1.1. They used highly heterogenous V beta chains for their T cell receptors. In addition to CD11ahighCD8+T cells, CD11ahighCD4+T cells were detected transiently after JHMV infection. The virus-specific cytotoxic T lymphocyte (CTL) activity was observed in both CD4+ and CD8+ spleen T cells from mice 7 days post-infection. The present study shows the dynamics of CD8+ and CD4+T cells in the spleen during JHMV infection in mice and suggests that CD11ahighT cells may be involved in JHMV clearance in vivo because their appearance was temporally correlated with T cell-mediated viral clearance in vivo and antiviral CTL activity in vitro.
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PMID:Characterization of T cells expanded in vivo during primary mouse hepatitis virus infection in mice. 874 3

We characterized liver-infiltrating leucocytes (LIL) from BALB/c and C57BL/6 mice 0-56 days after murine cytomegalovirus (MCMV) infection. Inflammation clears from C57BL/6 mice 4-5 weeks post infection (pi), but persists for several months in BALB/c mice. The LIL obtained were 60-80% Thy 1.2+ by flow cytometry. The percentage of CD8+ cells rose sharply in all mice 7 days pi, with little decrease in BALB/c mice by day 56. CD4-CD8-Thy 1.2+/TCR alpha beta + cells were more prevalent in LIL than lymph node cells (LNC) irrespective of MCMV infection, whilst infection increased the proportion of CD8+ L-selectin- LIL (but not LNC). LIL from both mouse strains demonstrated cytotoxic activity against YAC-1 cells, but only LIL from BALB/c mice proliferated spontaneously ex vivo 21 days pi, as measured by tritiated thymidine incorporation. BALB/c LIL produced IFN gamma and IgG2a 7-21 days pi, whilst IL-10 secretion was similar in both strains. Thus, persistent hepatitis in BALB/c mice is associated with activation and proliferation of intrahepatic leucocytes with some bias towards a Th1 response.
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PMID:Contrasting phenotypes of liver-infiltrating leucocytes isolated from MCMV-infected BALB/c and C57BL/6 mice. 961 48

Leukocyte infiltration into the liver is paramount to the development of liver injury in hepatitis. Hepatitis occurring after the administration of Con A in mice is felt to be a T lymphocyte-mediated disease. In this study, we report that neutrophils are the key initiators of lymphocyte recruitment and liver injury caused by Con A. The objectives of this study were to investigate the involvement of neutrophils in Con A-induced hepatitis in vivo via intravital microscopy. After Con A administration, we observed a significant increase in leukocyte rolling flux, a decrease in rolling velocity, and an increase in leukocyte adhesion to the hepatic microvasculature. Fluorescence microscopy identified that within 4 h of Con A administration only a minority of the recruited leukocytes were T lymphocytes. Furthermore, immunohistochemistry showed a significant increase in neutrophils recruited to the liver post-Con A treatment in association with liver cell damage, as reflected by elevated serum alanine aminotransferase levels. Using flow cytometry, we observed that Con A could bind directly to neutrophils, which resulted in a shedding of L-selectin, an increase in beta(2)-integrin expression, and the production of reactive oxidants. Following neutrophil depletion, a significant inhibition of Con A-induced CD4+ T lymphocyte recruitment to the liver resulted and complete reduction in hepatic injury, as assessed by serum alanine aminotransferase levels. In summary, the present data support the concept that neutrophils play an important and previously unrecognized role in governing Con A-induced CD4+ T cell recruitment to the liver and the subsequent development of hepatitis.
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PMID:Essential role for neutrophil recruitment to the liver in concanavalin A-induced hepatitis. 1468 8

Concanavalin A (Con A)-induced hepatitis is a model for human T cell-mediated hepatitis. We evaluated the role of L-selectin and intercellular adhesion molecule-1 (ICAM-1) in this model by injecting Con A intravenously in mice lacking L-selectin (L-selectin-/-), ICAM-1 (ICAM-1-/-), or both (L-selectin/ICAM-1-/-). Blood and liver samples were collected 0, 8, 24, and 48 h after Con A treatment. Increases in plasma transaminase levels, which peaked 8 h after injection, were reduced significantly in L-selectin-/-, ICAM-1-/-, and L-selectin/ICAM-1-/- mice compared with wild-type mice. Liver necrosis was more strongly inhibited in ICAM-1-/- mice than in L-selectin-/- mice but was most prominently reduced in L-selectin/ICAM-1-/- mice, in parallel with decreased plasma transaminase levels. The reduced severity of hepatitis in the mutant mice correlated with decreases in numbers of liver CD4+ T cells but not numbers of CD8+ T cells or neutrophils. Following Con A treatment, L-selectin deficiency reduced liver mRNA expression of tumor necrosis factor-alpha, and ICAM-1 deficiency reduced expression of interleukin-4. By contrast, reductions in liver macrophage inhibitor protein-1alpha mRNA occurred in all mutant mice. These results indicate that L-selectin and ICAM-1 contribute cooperatively to the development of Con A-induced hepatitis by regulating leukocyte infiltration and subsequent cytokine production.
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PMID:L-selectin and intercellular adhesion molecule-1 regulate the development of Concanavalin A-induced liver injury. 1646 40