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Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF.

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Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF. / Schümann, J; Angermüller, S; Bang, R; Lohoff, M; Tiegs, Gisa.

In: J IMMUNOL, Vol. 161, No. 10, 10, 1998, p. 5745-5754.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schümann, J, Angermüller, S, Bang, R, Lohoff, M & Tiegs, G 1998, 'Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF.', J IMMUNOL, vol. 161, no. 10, 10, pp. 5745-5754. <http://www.ncbi.nlm.nih.gov/pubmed/9820556?dopt=Citation>

APA

Schümann, J., Angermüller, S., Bang, R., Lohoff, M., & Tiegs, G. (1998). Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF. J IMMUNOL, 161(10), 5745-5754. [10]. http://www.ncbi.nlm.nih.gov/pubmed/9820556?dopt=Citation

Vancouver

Schümann J, Angermüller S, Bang R, Lohoff M, Tiegs G. Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF. J IMMUNOL. 1998;161(10):5745-5754. 10.

Bibtex

@article{7536ac6d2e444dfd8be8ffd25bc39beb,
title = "Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF.",
abstract = "The most potent virulence factor of Pseudomonas aeruginosa, its exotoxin A (PEA), inhibits protein synthesis, especially in the liver, and is a weak T cell mitogen. This study was performed to correlate hepatotoxic and possible immunostimulatory features of PEA in vivo. Injection of PEA to mice caused hepatocyte apoptosis, an increase in plasma transaminase activities, and the release of TNF, IFN-gamma, IL-2, and IL-6 into the circulation. Most strikingly, liver damage depended on T cells. Athymic nude mice or mice depleted of T cells by anti-Thy1.2 mAb pretreatment failed to develop acute hepatic failure, and survival was significantly prolonged following T cell depletion. Neutralization of TNF or lack of TNF receptors prevented liver injury. In the liver, TNF was produced by Kupffer cells before hepatocellular death occurred. After T cell depletion, Kupffer cells failed to produce TNF. Transaminase release was significantly reduced in perforin knockout mice, and it was even elevated in lpr/lpr mice. These results demonstrate that PEA induces liver damage not only by protein synthesis inhibition but also by TNF- and perforin-dependent, Fas-independent, apoptotic signals.",
keywords = "Animals, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Acute Disease, Mice, Inbred Strains, Mice, Nude, Injections, Intravenous, Cytokines/metabolism, Bacterial Toxins/*toxicity, Exotoxins/*toxicity, *ADP Ribose Transferases, *Virulence Factors, Liver/pathology/ultrastructure, Liver Diseases/immunology/*pathology, Mice, Inbred C3H, Mice, Inbred MRL lpr, Pseudomonas Infections/immunology/*pathology, Pseudomonas aeruginosa/*immunology, T-Lymphocytes/*immunology, Tumor Necrosis Factor-alpha/*immunology, Animals, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Acute Disease, Mice, Inbred Strains, Mice, Nude, Injections, Intravenous, Cytokines/metabolism, Bacterial Toxins/*toxicity, Exotoxins/*toxicity, *ADP Ribose Transferases, *Virulence Factors, Liver/pathology/ultrastructure, Liver Diseases/immunology/*pathology, Mice, Inbred C3H, Mice, Inbred MRL lpr, Pseudomonas Infections/immunology/*pathology, Pseudomonas aeruginosa/*immunology, T-Lymphocytes/*immunology, Tumor Necrosis Factor-alpha/*immunology",
author = "J Sch{\"u}mann and S Angerm{\"u}ller and R Bang and M Lohoff and Gisa Tiegs",
year = "1998",
language = "English",
volume = "161",
pages = "5745--5754",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

RIS

TY - JOUR

T1 - Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF.

AU - Schümann, J

AU - Angermüller, S

AU - Bang, R

AU - Lohoff, M

AU - Tiegs, Gisa

PY - 1998

Y1 - 1998

N2 - The most potent virulence factor of Pseudomonas aeruginosa, its exotoxin A (PEA), inhibits protein synthesis, especially in the liver, and is a weak T cell mitogen. This study was performed to correlate hepatotoxic and possible immunostimulatory features of PEA in vivo. Injection of PEA to mice caused hepatocyte apoptosis, an increase in plasma transaminase activities, and the release of TNF, IFN-gamma, IL-2, and IL-6 into the circulation. Most strikingly, liver damage depended on T cells. Athymic nude mice or mice depleted of T cells by anti-Thy1.2 mAb pretreatment failed to develop acute hepatic failure, and survival was significantly prolonged following T cell depletion. Neutralization of TNF or lack of TNF receptors prevented liver injury. In the liver, TNF was produced by Kupffer cells before hepatocellular death occurred. After T cell depletion, Kupffer cells failed to produce TNF. Transaminase release was significantly reduced in perforin knockout mice, and it was even elevated in lpr/lpr mice. These results demonstrate that PEA induces liver damage not only by protein synthesis inhibition but also by TNF- and perforin-dependent, Fas-independent, apoptotic signals.

AB - The most potent virulence factor of Pseudomonas aeruginosa, its exotoxin A (PEA), inhibits protein synthesis, especially in the liver, and is a weak T cell mitogen. This study was performed to correlate hepatotoxic and possible immunostimulatory features of PEA in vivo. Injection of PEA to mice caused hepatocyte apoptosis, an increase in plasma transaminase activities, and the release of TNF, IFN-gamma, IL-2, and IL-6 into the circulation. Most strikingly, liver damage depended on T cells. Athymic nude mice or mice depleted of T cells by anti-Thy1.2 mAb pretreatment failed to develop acute hepatic failure, and survival was significantly prolonged following T cell depletion. Neutralization of TNF or lack of TNF receptors prevented liver injury. In the liver, TNF was produced by Kupffer cells before hepatocellular death occurred. After T cell depletion, Kupffer cells failed to produce TNF. Transaminase release was significantly reduced in perforin knockout mice, and it was even elevated in lpr/lpr mice. These results demonstrate that PEA induces liver damage not only by protein synthesis inhibition but also by TNF- and perforin-dependent, Fas-independent, apoptotic signals.

KW - Animals

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Acute Disease

KW - Mice, Inbred Strains

KW - Mice, Nude

KW - Injections, Intravenous

KW - Cytokines/metabolism

KW - Bacterial Toxins/toxicity

KW - Exotoxins/toxicity

KW - ADP Ribose Transferases

KW - Virulence Factors

KW - Liver/pathology/ultrastructure

KW - Liver Diseases/immunology/pathology

KW - Mice, Inbred C3H

KW - Mice, Inbred MRL lpr

KW - Pseudomonas Infections/immunology/pathology

KW - Pseudomonas aeruginosa/immunology

KW - T-Lymphocytes/immunology

KW - Tumor Necrosis Factor-alpha/immunology

KW - Animals

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Acute Disease

KW - Mice, Inbred Strains

KW - Mice, Nude

KW - Injections, Intravenous

KW - Cytokines/metabolism

KW - Bacterial Toxins/toxicity

KW - Exotoxins/toxicity

KW - ADP Ribose Transferases

KW - Virulence Factors

KW - Liver/pathology/ultrastructure

KW - Liver Diseases/immunology/pathology

KW - Mice, Inbred C3H

KW - Mice, Inbred MRL lpr

KW - Pseudomonas Infections/immunology/pathology

KW - Pseudomonas aeruginosa/immunology

KW - T-Lymphocytes/immunology

KW - Tumor Necrosis Factor-alpha/immunology

M3 - SCORING: Journal article

VL - 161

SP - 5745

EP - 5754

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 10

M1 - 10

ER -