Abstract
Concanavalin A (Con A)-induced hepatitis has been investigated as a model of T cell-mediated liver injury, in which IFN-gamma plays an essential role by inducing apoptosis of liver cells. Since a large number of neutrophils infiltrate into the liver in the model, the role of neutrophils was investigated in this study. Con A hardly caused liver injury in neutrophil-depleted mice, as assessed as to the plasma alanine aminotransferase level as well as histochemistry. Neutrophil-depleted mice also failed to produce IFN-gamma. Intracellular IFN-gamma staining revealed that, among liver leukocytes, T and NK cells but not neutrophils are the main producers of IFN-gamma. Nylon wool-purified "T cells", however, failed to produce IFN-gamma in response to Con A in vitro, while the production was restored by the addition of neutrophils. Overall, this study suggests that neutrophils play a novel accessory role in IFN-gamma production in Con A-induced hepatitis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alanine Transaminase / blood
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Animals
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Movement / physiology
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Chemical and Drug Induced Liver Injury / etiology*
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Chemical and Drug Induced Liver Injury / immunology
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Chemical and Drug Induced Liver Injury / pathology
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Coculture Techniques
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Concanavalin A / pharmacology
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Concanavalin A / toxicity*
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Disease Models, Animal
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Interferon-gamma / blood
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Interferon-gamma / immunology
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Interferon-gamma / metabolism*
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Interleukin-4 / blood
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism
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Leukocyte Reduction Procedures
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Leukocytes / drug effects
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Leukocytes / immunology
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Leukocytes / metabolism
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Liver / drug effects
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Liver / immunology
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Liver / pathology
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Male
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Mice
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Mice, Inbred C3H
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Neutrophils / immunology*
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Neutrophils / metabolism
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Tumor Necrosis Factor-alpha
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Concanavalin A
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Interleukin-4
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Interferon-gamma
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Alanine Transaminase