The pore-forming protein epsilon toxin (Etx) from Clostridium perfringens produces acute perivascular edema affecting several organs, especially the brain and lungs. Despite the toxin evident effect on microvasculature and endothelial cells, the underlying molecular and cellular mechanisms remain obscure. Moreover, no Etx-sensitive endothelial cell model has been identified to date. Here, we characterize the mouse lung endothelial cell line 1G11 as an Etx-sensitive cell line and compare it with the well-characterized Etx-sensitive Madin-Darby canine kidney epithelial cell line. Several experimental approaches, including morphological and cytotoxic assays, clearly demonstrate that the 1G11 cell line is highly sensitive to Etx and show the specific binding, oligomerization, and pore-forming activity of the toxin in these cells. Recently, the myelin and lymphocyte (MAL) protein has been postulated as a putative receptor for Etx. Here, we show the presence of Mal mRNA in the 1G11 cell line and the presence of the MAL protein in the endothelium of some mouse lung vessels, supporting the hypothesis that this protein is a key element in the Etx intoxication pathway. The existence of an Etx-sensitive cell line of endothelial origin would help shed light on the cellular and molecular mechanisms underlying Etx-induced edema and its consequences.

中文翻译：

---

肺内皮细胞对产气荚膜梭状芽胞杆菌的ε毒素敏感。

来自产气荚膜梭状芽胞杆菌的成孔蛋白ε毒素（Etx）产生急性血管周水肿，影响几个器官，尤其是脑和肺。尽管毒素对微血管和内皮细胞有明显作用，但潜在的分子和细胞机制仍然不清楚。此外，迄今为止尚未鉴定出对Etx敏感的内皮细胞模型。在这里，我们将小鼠肺内皮细胞系1G11表征为对Etx敏感的细胞系，并将其与特征明确的对Etx敏感的Madin-Darby犬肾上皮细胞系进行比较。包括形态学和细胞毒性测定在内的几种实验方法清楚地表明1G11细胞系对Etx高度敏感，并显示了这些细胞中毒素的特异性结合，寡聚和成孔活性。最近，髓磷脂和淋巴细胞（MAL）蛋白被认为是Etx的假定受体。在这里，我们显示了1G11细胞系中Mal mRNA的存在以及某些小鼠肺血管内皮中MAL蛋白的存在，支持了这一蛋白是Etx中毒途径中关键要素的假设。内皮来源的Etx敏感细胞系的存在将有助于阐明Etx诱导的水肿及其后果的细胞和分子机制。