A novel mechanism of murine hepatocyte death inducible by Concanavalin A

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Leist_M_J_Hepatol_1996.pdf
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1996
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Leist, Marcel
Wendel, Albrecht
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Background: Concanavalin A (Con A) is a plant lectin that polyclonally activates T-cells. When given intravenously to mice it induces a selective liver failure. Hepatotoxicity following Con A administration involves the systemic release of tumor necrosis factor.
Methods: We used primary murine hepatocyte cultures to investigate mechanisms of hepatocytotoxicity related to this animal model of inflammatory liver failure.
Results: Con A was directly toxic for cultured hepatocytes. This toxicity did not require additional cytokines or the presence of T cells. Cytotoxicity due to Con A involved specific binding of the lectin to mannosyl cell surface receptors, but no internalization. Other structurally similar lectins lacked such an in vitro hepatocytotoxicity. Con A induced initially reversible alterations of the morphology that were different from the ones caused by classical hepatotoxins. Con A-induced cell death was highly specific for murine hepatocytes. It was neither apoptotic by morphology nor did it involve DNA fragmentation. In addition, Con A caused a fall in cellular total glutathione content and an increase in transcriptional activity. Stabilization of microtubules by taxol completely protected cells from the lectin.
Conclusions: Stimulation of hepatocytes with Con A elicits a novel mechanism of cytotoxicity due to inappropriate excessive stimulation of membrane receptors and subsequent disturbance of the cytoskeleton.

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570 Biowissenschaften, Biologie
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Cytotoxity, Glutathione, Lectin, Liver, Taxol
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ISO 690LEIST, Marcel, Albrecht WENDEL, 1996. A novel mechanism of murine hepatocyte death inducible by Concanavalin A. In: Journal of Hepatology. 1996, 25(6), pp. 948-959. ISSN 0168-8278. Available under: doi: 10.1016/S0168-8278(96)80301-1
BibTex
@article{Leist1996novel-7152,
  year={1996},
  doi={10.1016/S0168-8278(96)80301-1},
  title={A novel mechanism of murine hepatocyte death inducible by Concanavalin A},
  number={6},
  volume={25},
  issn={0168-8278},
  journal={Journal of Hepatology},
  pages={948--959},
  author={Leist, Marcel and Wendel, Albrecht}
}
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