Clostridium botulinum serotype D neurotoxin and toxin complex bind to bovine aortic endothelial cells via sialic acid.
Clostridium botulinum serotype D neurotoxin and toxin complex bind to bovine aortic endothelial cells via sialic acid.
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DOI：
10.1111/j.1574-695x.2008.00475.x
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发表时间：
2008-12
影响因子：
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通讯作者：
T. Yoneyama;Keita Miyata;T. Chikai;A. Mikami;Tomonori Suzuki;Kimiko Hasegawa;T. Ikeda;Toshihiro Watanabe;T. Ohyama;K. Niwa
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文献类型：
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作者：
T. Yoneyama;Keita Miyata;T. Chikai;A. Mikami;Tomonori Suzuki;Kimiko Hasegawa;T. Ikeda;Toshihiro Watanabe;T. Ohyama;K. Niwa
肉毒神经毒素（BoNT）是一种大毒素复合物（L-TC），与无毒的非血凝素（NTNHA）和三种血凝素亚组分（HA-70、-33和-17）结合。BoNT与神经元和L-TC与肠上皮细胞的结合特性已得到充分证实，而与其他组织的结合特性在很大程度上尚不清楚。在这里，获得新的见解食源性肉毒中毒的发病机制，我们研究是否肉毒杆菌毒素结合血管内皮细胞。将肉毒梭菌血清型D的BoNT和750 kDa L-TC（BoNT、NTNHA和HA的复合物）与牛主动脉内皮细胞（BAECs）孵育，并使用十二烷基硫酸钠聚丙烯酰胺凝胶电泳和Western印迹评估与细胞的结合。BoNT和L-TC均与BAEC结合，L-TC显示更强的结合。BoNT和L-TC与BAECs的结合被细胞培养基中的N-乙酰神经氨酸或用神经氨酸酶处理的细胞显著抑制。然而，半乳糖，乳糖或N-乙酰半乳糖胺没有显着抑制毒素结合细胞。这是第一份证明BoNT和L-TC通过唾液酸与BAECs结合的报告，这一机制可能在食物中毒中BoNT的运输途径中很重要。
Botulinum neurotoxin (BoNT) is produced as a large toxin complex (L-TC) associated with nontoxic nonhemagglutinin (NTNHA) and three hemagglutinin subcomponents (HA-70, -33 and -17). The binding properties of BoNT to neurons and L-TC to intestinal epithelial cells are well documented, while those to other tissues are largely unknown. Here, to obtain novel insights into the pathogenesis of foodborne botulism, we examine whether botulinum toxins bind to vascular endothelial cells. BoNT and 750 kDa L-TC (a complex of BoNT, NTNHA and HAs) of Clostridium botulinum serotype D were incubated with bovine aortic endothelial cells (BAECs), and binding to the cells was assessed using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot. Both BoNT and L-TC bound to BAECs, with L-TC showing stronger binding. Binding of BoNT and L-TC to BAECs was significantly inhibited by N-acetyl neuraminic acid in the cell culture medium or by treatment of the cells with neuraminidase. However, galactose, lactose or N-acetyl galactosamine did not significantly inhibit toxin binding to the cells. This is the first report demonstrating that BoNT and L-TC bind to BAECs via sialic acid, and this mechanism may be important in the trafficking pathway of BoNT in foodborne botulism.