Document Detail

A novel mechanism of murine hepatocyte death inducible by concanavalin A.
MedLine Citation:
PMID:  9007725     Owner:  NLM     Status:  MEDLINE    
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.
M Leist; A Wendel
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of hepatology     Volume:  25     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  1996 Dec 
Date Detail:
Created Date:  1997-04-09     Completed Date:  1997-04-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  948-59     Citation Subset:  IM    
Faculty of Biology, University of Konstanz, Germany.
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MeSH Terms
Antineoplastic Agents, Phytogenic / pharmacology
Cell Death / drug effects
Cells, Cultured
Concanavalin A / metabolism,  toxicity*
Enzyme-Linked Immunosorbent Assay
Glutathione / metabolism
Lectins, C-Type*
Liver / drug effects*,  metabolism,  ultrastructure
Mannose-Binding Lectins*
Mice, Inbred BALB C
Microscopy, Electron, Scanning
Microtubules / drug effects
Paclitaxel / pharmacology
Receptors, Cell Surface / metabolism
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Lectins, C-Type; 0/Mannose-Binding Lectins; 0/Receptors, Cell Surface; 0/mannose receptor; 11028-71-0/Concanavalin A; 33069-62-4/Paclitaxel; 70-18-8/Glutathione

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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