A novel mechanism of murine hepatocyte death inducible by Concanavalin A

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LEIST, Marcel, Albrecht WENDEL, 1996. A novel mechanism of murine hepatocyte death inducible by Concanavalin A. In: Journal of Hepatology. 25(6), pp. 948-959. ISSN 0168-8278

@article{Leist1996novel-7152, title={A novel mechanism of murine hepatocyte death inducible by Concanavalin A}, year={1996}, doi={10.1016/S0168-8278(96)80301-1}, number={6}, volume={25}, issn={0168-8278}, journal={Journal of Hepatology}, pages={948--959}, author={Leist, Marcel and Wendel, Albrecht} }

Leist, Marcel 1996 A novel mechanism of murine hepatocyte death inducible by Concanavalin A First publ. in: Journal of Hepatology 25 (1996), 6, pp. 948-959 eng Wendel, Albrecht Leist, Marcel Wendel, Albrecht 2011-03-24T17:32:15Z 2011-03-24T17:32:15Z application/pdf deposit-license 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.<br />Methods: We used primary murine hepatocyte cultures to investigate mechanisms of hepatocytotoxicity related to this animal model of inflammatory liver failure.<br />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.<br />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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