Enhanced activation of Gb3-bound Shiga toxin by leptin induced after infection with STEC O157

口服感染产志贺毒素(STX)的大肠杆菌可引起蛋白质营养不良小鼠的急性脑病。感染后18h内可诱导感染小鼠血中肿瘤坏死因子-α和瘦素水平升高。在血液中这两种可溶性因子升高后，脑组织中的凋亡细胞数量增加。相比之下，感染不产生STX的大肠杆菌不会引起这种变化。瘦素处理诱导培养的神经细胞在与STX孵育后产生高水平的肿瘤坏死因子-α和NO。瘦素可引起非脂筏细胞ABCA1的表达增加，这可能与脂筏中的α分子增多以及细胞内吞Gb3结合的STx有关。这些变化可能与STX诱导的神经细胞凋亡增强有关。然而，血管内细胞没有观察到这种增强。尽管瘦素增加神经细胞对STX敏感性的确切机制，但目前的发现可能解释了不同个体对STEC感染的不同敏感性。

Oral infection with Shiga toxin (Stx) -producing E. coil resulted in acute encephalopathy in protein malnutrition mice. The infection induced TNF-α and leptin in the blood of infected mice within 18 h of infection. After the elevation of these two soluble factors in the blood, the number of apoptotic cells in the brain increased. In contrast, infection with Stx-nonproducing E. coli did not induce such changes. Treatment with leptin induced high levels of TNF-α and NO production from cultured neuronal cells after incubation with Stx. Treatment with leptin caused the increase in ABCA1 in non-rafts of TNF-α-stimulated neuronal cells, which was associated with the increase in Gb3 molecules in lipid rafts as well as endocytosis of Gb3-bound Stx by the cells. These changes seemed to be related to the enhancement of Stx-induced apoptosis of neuronal cells. However, such enhancement was not observed for endovascular cells. The present findings may account for the different sensitivity to STEC infection among individuals, though the precise mechanism of how leptin increases Stx sensitivity of neuronal cells.