Epsilon toxin (ETX) is a 33‐kDa pore‐forming toxin produced by type B and D strains of Clostridium perfringens . We previously found that ETX caused haemolysis of human red blood cells, but not of erythrocytes from other species. The cellular and molecular mechanisms of ETX‐mediated haemolysis are not well understood. Here, we investigated the effects of ETX on erythrocyte volume and the role of the putative myelin and lymphocyte (MAL) receptors in ETX‐mediated haemolysis. We observed that ETX initially decreased erythrocyte size, followed by a gradual increase in volume until lysis. Moreover, ETX triggered phosphatidylserine (PS) exposure and enhanced ceramide abundance in erythrocytes. Cell shrinkage, PS exposure and enhanced ceramide abundance were preceded by increases in intracellular Ca²⁺ concentration. Interestingly, lentivirus‐mediated RNA interference studies in the human erythroleukaemia cell line (HEL) cells confirmed that MAL contributes to ETX‐induced cytotoxicity. Additionally, ETX was shown to bind to MAL in vitro. The results of this study recommend that ETX‐mediated haemolysis is associated with MAL receptor activation in human erythrocytes. These data imply that interventions affecting local MAL‐mediated autocrine and paracrine signalling may prevent ETX‐mediated erythrocyte damage.

中文翻译：

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产气荚膜梭菌ε毒素与红细胞MAL受体结合并触发磷脂酰丝氨酸暴露。

Epsilon毒素（ETX）是由产气荚膜梭菌B型和D型菌株产生的33 kDa的成孔毒素。我们先前发现，ETX引起人类红细胞的溶血，但未引起其他物种的红细胞的溶血。ETX介导的溶血作用的细胞和分子机制尚不清楚。在这里，我们研究了ETX对红细胞体积的影响以及在ETX介导的溶血中假定的髓鞘和淋巴细胞（MAL）受体的作用。我们观察到，ETX最初会减少红细胞的大小，然后逐渐增加其体积直至溶解。此外，ETX触发了磷脂酰丝氨酸（PS）暴露并增强了红细胞中神经酰胺的丰度。细胞缩小，PS暴露和神经酰胺丰度增强之前，细胞内Ca ²⁺升高浓度。有趣的是，在人类红白血病细胞系（HEL）细胞中慢病毒介导的RNA干扰研究证实MAL有助于ETX诱导的细胞毒性。另外，显示ETX在体外结合MAL。这项研究的结果建议，ETX介导的溶血与人类红细胞中的MAL受体激活有关。这些数据表明，影响局部MAL介导的自分泌和旁分泌信号传导的干预措施可以预防ETX介导的红细胞损害。