Leist M, Wendel A
Faculty of Biology, University of Konstanz, Germany.
J Hepatol. 1996 Dec;25(6):948-59. doi: 10.1016/s0168-8278(96)80301-1.
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.
We used primary murine hepatocyte cultures to investigate mechanisms of hepatocytotoxicity related to this animal model of inflammatory liver failure.
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.
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.
伴刀豆球蛋白A（Con A）是一种能多克隆激活T细胞的植物凝集素。给小鼠静脉注射时，它会诱发选择性肝衰竭。Con A给药后的肝毒性涉及肿瘤坏死因子的全身释放。
我们使用原代小鼠肝细胞培养物来研究与这种炎症性肝衰竭动物模型相关的肝细胞毒性机制。
Con A对培养的肝细胞具有直接毒性。这种毒性不需要额外的细胞因子或T细胞的存在。Con A引起的细胞毒性涉及凝集素与甘露糖基细胞表面受体的特异性结合，但不会内化。其他结构相似的凝集素缺乏这种体外肝细胞毒性。Con A最初诱导的形态学改变是可逆的，与经典肝毒素引起的改变不同。Con A诱导的细胞死亡对小鼠肝细胞具有高度特异性。从形态学上看，它既不是凋亡性的，也不涉及DNA片段化。此外，Con A导致细胞总谷胱甘肽含量下降和转录活性增加。紫杉醇使微管稳定，完全保护细胞免受凝集素的影响。
用Con A刺激肝细胞会引发一种新的细胞毒性机制，这是由于膜受体受到不适当的过度刺激以及随后细胞骨架受到干扰所致。
