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Induction of murine liver damage by overexpression of CD40 ligand provides an experimental model to study fulminant hepatic failure

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Induction of murine liver damage by overexpression of CD40 ligand provides an experimental model to study fulminant hepatic failure. / Schmitz, Volker; Dombrowski, Frank; Prieto, Jesús; Qian, Cheng; Diehl, Linda; Knolle, Percy; Sauerbruch, Tilman; Caselmann, Wolfgang H; Spengler, Ulrich; Leifeld, Ludger.

In: HEPATOLOGY, Vol. 44, No. 2, 08.2006, p. 430-9.

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

Harvard

Schmitz, V, Dombrowski, F, Prieto, J, Qian, C, Diehl, L, Knolle, P, Sauerbruch, T, Caselmann, WH, Spengler, U & Leifeld, L 2006, 'Induction of murine liver damage by overexpression of CD40 ligand provides an experimental model to study fulminant hepatic failure', HEPATOLOGY, vol. 44, no. 2, pp. 430-9. https://doi.org/10.1002/hep.21274

APA

Schmitz, V., Dombrowski, F., Prieto, J., Qian, C., Diehl, L., Knolle, P., Sauerbruch, T., Caselmann, W. H., Spengler, U., & Leifeld, L. (2006). Induction of murine liver damage by overexpression of CD40 ligand provides an experimental model to study fulminant hepatic failure. HEPATOLOGY, 44(2), 430-9. https://doi.org/10.1002/hep.21274

Vancouver

Schmitz V, Dombrowski F, Prieto J, Qian C, Diehl L, Knolle P et al. Induction of murine liver damage by overexpression of CD40 ligand provides an experimental model to study fulminant hepatic failure. HEPATOLOGY. 2006 Aug;44(2):430-9. https://doi.org/10.1002/hep.21274

Bibtex

@article{f9eacd3ad56446e0abd1cab41cc26333,
title = "Induction of murine liver damage by overexpression of CD40 ligand provides an experimental model to study fulminant hepatic failure",
abstract = "Previously, we demonstrated that intrahepatic upregulation of the immunoactivating molecules CD40 and CD40 ligand (CD40L) are early mechanisms for liver cell damage in human and murine fulminant hepatic failure (FHF). In the present study, we investigated the functional effects of intrahepatic overexpression of CD40L by adenoviral-mediated gene transfer (AdCD40L) in mice. AdCD40L injection induced severe liver cell damage, which was associated with increased alanine aminotransferase (ALT) levels peaking at day 5 after vector administration (AdCD40L, 1,707 +/- 279 U/L; AdLacZ, 213 +/- 25 U/L) and with lethality in half of the mice. Except for mild splenomegaly, no organs other than the liver were involved in inflammatory reactions. CD40-CD40L interaction was mandatory for liver damage, because CD40(-/-) mice were completely protected. Furthermore, CD40L-induced FHF depended on competent lymphocytes, because inflammatory reactions were strongly decreased in SCID and Rag1(-/-) mice. In contrast, neither natural killer T (NKT) cells nor Kupffer cells relevantly influenced histology as shown in NKT cell-deficient CD1d(-/-) mice and by gadolinium depletion of Kupffer cells. Furthermore, immunosuppression by dexamethasone and cyclosporin A was not sufficient to block CD40L damage. In conclusion, we present a model of FHF with strong similarities to human FHF with respect to time course and histological changes. This model suggests involvement of the CD40-CD40L system in FHF and might have important implications for future pathophysiological studies of this condition.",
keywords = "Adenoviridae, Animals, Antigens, CD40, CD40 Ligand, Disease Models, Animal, Disease Progression, Follow-Up Studies, Gene Transfer Techniques, Genetic Vectors, Liver Failure, Acute, Male, Mice, Mice, Inbred BALB C, Mice, SCID",
author = "Volker Schmitz and Frank Dombrowski and Jes{\'u}s Prieto and Cheng Qian and Linda Diehl and Percy Knolle and Tilman Sauerbruch and Caselmann, {Wolfgang H} and Ulrich Spengler and Ludger Leifeld",
year = "2006",
month = aug,
doi = "10.1002/hep.21274",
language = "English",
volume = "44",
pages = "430--9",
journal = "HEPATOLOGY",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

RIS

TY - JOUR

T1 - Induction of murine liver damage by overexpression of CD40 ligand provides an experimental model to study fulminant hepatic failure

AU - Schmitz, Volker

AU - Dombrowski, Frank

AU - Prieto, Jesús

AU - Qian, Cheng

AU - Diehl, Linda

AU - Knolle, Percy

AU - Sauerbruch, Tilman

AU - Caselmann, Wolfgang H

AU - Spengler, Ulrich

AU - Leifeld, Ludger

PY - 2006/8

Y1 - 2006/8

N2 - Previously, we demonstrated that intrahepatic upregulation of the immunoactivating molecules CD40 and CD40 ligand (CD40L) are early mechanisms for liver cell damage in human and murine fulminant hepatic failure (FHF). In the present study, we investigated the functional effects of intrahepatic overexpression of CD40L by adenoviral-mediated gene transfer (AdCD40L) in mice. AdCD40L injection induced severe liver cell damage, which was associated with increased alanine aminotransferase (ALT) levels peaking at day 5 after vector administration (AdCD40L, 1,707 +/- 279 U/L; AdLacZ, 213 +/- 25 U/L) and with lethality in half of the mice. Except for mild splenomegaly, no organs other than the liver were involved in inflammatory reactions. CD40-CD40L interaction was mandatory for liver damage, because CD40(-/-) mice were completely protected. Furthermore, CD40L-induced FHF depended on competent lymphocytes, because inflammatory reactions were strongly decreased in SCID and Rag1(-/-) mice. In contrast, neither natural killer T (NKT) cells nor Kupffer cells relevantly influenced histology as shown in NKT cell-deficient CD1d(-/-) mice and by gadolinium depletion of Kupffer cells. Furthermore, immunosuppression by dexamethasone and cyclosporin A was not sufficient to block CD40L damage. In conclusion, we present a model of FHF with strong similarities to human FHF with respect to time course and histological changes. This model suggests involvement of the CD40-CD40L system in FHF and might have important implications for future pathophysiological studies of this condition.

AB - Previously, we demonstrated that intrahepatic upregulation of the immunoactivating molecules CD40 and CD40 ligand (CD40L) are early mechanisms for liver cell damage in human and murine fulminant hepatic failure (FHF). In the present study, we investigated the functional effects of intrahepatic overexpression of CD40L by adenoviral-mediated gene transfer (AdCD40L) in mice. AdCD40L injection induced severe liver cell damage, which was associated with increased alanine aminotransferase (ALT) levels peaking at day 5 after vector administration (AdCD40L, 1,707 +/- 279 U/L; AdLacZ, 213 +/- 25 U/L) and with lethality in half of the mice. Except for mild splenomegaly, no organs other than the liver were involved in inflammatory reactions. CD40-CD40L interaction was mandatory for liver damage, because CD40(-/-) mice were completely protected. Furthermore, CD40L-induced FHF depended on competent lymphocytes, because inflammatory reactions were strongly decreased in SCID and Rag1(-/-) mice. In contrast, neither natural killer T (NKT) cells nor Kupffer cells relevantly influenced histology as shown in NKT cell-deficient CD1d(-/-) mice and by gadolinium depletion of Kupffer cells. Furthermore, immunosuppression by dexamethasone and cyclosporin A was not sufficient to block CD40L damage. In conclusion, we present a model of FHF with strong similarities to human FHF with respect to time course and histological changes. This model suggests involvement of the CD40-CD40L system in FHF and might have important implications for future pathophysiological studies of this condition.

KW - Adenoviridae

KW - Animals

KW - Antigens, CD40

KW - CD40 Ligand

KW - Disease Models, Animal

KW - Disease Progression

KW - Follow-Up Studies

KW - Gene Transfer Techniques

KW - Genetic Vectors

KW - Liver Failure, Acute

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, SCID

U2 - 10.1002/hep.21274

DO - 10.1002/hep.21274

M3 - SCORING: Journal article

C2 - 16871541

VL - 44

SP - 430

EP - 439

JO - HEPATOLOGY

JF - HEPATOLOGY

SN - 0270-9139

IS - 2

ER -