Bartels F, Bigalke H
Department of Pharmacology and Toxicology, Medical School of Hannover, Germany.
Infect Immun. 1992 Jan;60(1):302-7. doi: 10.1128/iai.60.1.302-307.1992.
Tetanus toxin blocks carbachol-stimulated release of noradrenaline from bovine adrenal chromaffin cells in culture, provided it can gain access to the cells. This can be achieved by electropermeabilization of the plasma membrane or by enriching the membrane with exogenous gangliosides which serve as carriers of the toxin. The inhibition of noradrenaline release persists for at least 6 days, even in the presence of specific anti-tetanus toxin antibodies in the culture medium. However, the block is preventable, for the most part, when antibodies enter chromaffin cells during electropermeabilization, before the uptake of the toxin is facilitated by inserting exogenous gangliosides into the plasma membrane 2 days later. This indicates that the antibodies pass into the cells through the physically induced pores and that these intracellular antibodies neutralize incoming tetanus toxin. If, on the other hand, exocytosis has been inhibited by tetanus toxin, it will recover within 3 days, provided specific anti-tetanus toxin antibodies are introduced into the cells by electropermeabilization. The recovery is not linked to a specific route of entry of the toxin. It is concluded that the restoration of noradrenaline release requires not only the intracellular neutralization of tetanus toxin but also the reconstitution of the as yet unknown target molecule of the toxin.
破伤风毒素可阻断培养的牛肾上腺嗜铬细胞中卡巴胆碱刺激的去甲肾上腺素释放,前提是它能够进入细胞。这可以通过对质膜进行电通透处理或通过用作为毒素载体的外源性神经节苷脂富集膜来实现。即使培养基中存在特异性抗破伤风毒素抗体,去甲肾上腺素释放的抑制仍持续至少6天。然而,当抗体在电通透处理期间进入嗜铬细胞时,在两天后通过将外源性神经节苷脂插入质膜促进毒素摄取之前,这种阻断在很大程度上是可以预防的。这表明抗体通过物理诱导的孔进入细胞,并且这些细胞内抗体中和进入的破伤风毒素。另一方面,如果破伤风毒素抑制了胞吐作用,只要通过电通透处理将特异性抗破伤风毒素抗体引入细胞,它将在3天内恢复。恢复与毒素进入的特定途径无关。得出的结论是,去甲肾上腺素释放的恢复不仅需要细胞内对破伤风毒素的中和,还需要毒素尚未知的靶分子的重构。