Clostridium perfringens type A-induced gas gangrene is characterized by severe myonecrosis, and α-toxin has been revealed to be a major virulence factor involved in the pathogenesis. However, the detailed mechanism is unclear. Here, we show that CD31⁺ endothelial cell counts decrease in muscles infected with C. perfringens in an α-toxin-dependent manner. In vitro experiments revealed that α-toxin preferentially and rapidly induces the death of human umbilical vein endothelial cells (HUVECs) compared with C2C12 murine muscle cells. The toxin induces apoptosis of HUVECs by increasing ceramide. Furthermore, the specificity might be dependent on differences in the sensitivity to ceramide between these cell lines. Together, our results suggest that α-toxin-induced endothelial cell death promotes severe myonecrosis and is involved in the pathogenesis of C. perfringens.

产气荚膜梭状芽孢杆菌引起的A型气坏疽的特征是严重的肌坏死，并且α毒素已被证明是发病机理中的主要毒力因子。但是，具体机制尚不清楚。在这里，我们显示感染了产气荚膜梭菌的肌肉中CD31 ⁺内皮细胞计数以α-毒素依赖性方式降低。体外实验表明，与C2C12鼠肌细胞相比，α毒素优先快速地诱导人脐静脉内皮细胞（HUVEC）死亡。该毒素通过增加神经酰胺诱导HUVEC的凋亡。此外，特异性可能取决于这些细胞系之间对神经酰胺的敏感性差异。在一起，我们的结果表明α-毒素诱导的内皮细胞死亡促进严重的肌坏死并参与产气荚膜梭菌的发病机理。