Ashkenazi S, Yuhas Y, Even-Tov S, Kaminsky E, Danon Y L
Children's Medical Center of Israel, Petah Tikva.
Isr J Med Sci. 1994 Aug;30(8):604-10.
Although neurologic manifestations are frequent during childhood shigellosis, their pathogenesis is unclear and controversial. Shiga toxin and other cytotoxins are often implicated, but their effect on neuronal cells has not been determined. We examined the effect of purified Shiga toxin and sonicates of Shigella isolates from children with neurologic symptoms on well-characterized human neuroblastoma cells in vitro. Quantitative determinations showed high cytotoxicity of Shiga toxin on HeLa cells (1.2 x 10(6) CD50/mg purified toxin), but no effect on LA-N-1, LA-N-5 and IMR neuroblastoma cell lines. Pretreatment with tumor necrosis factor, which increases expression of the Shiga toxin receptor, globotriosyl ceramide, in endothelial cells and enhanced Shiga toxin cytotoxicity, did not affect the susceptibility of neuroblastoma cells to the toxin. Low dilutions (up to 1:16-1:64) of sonicates of Shigella isolates from children with neurologic symptoms caused agglutination of neuroblastoma cells, but no cell killing was observed morphologically. This study shows that Shiga toxin does not exhibit cytotoxic activity on the human neuroblastoma cell lines examined, neither do sonicates of relevant Shigella strains. The mechanism and significance of the agglutination activity on neuroblastoma cells should be further studied.
尽管在儿童志贺菌病期间神经学表现很常见，但其发病机制尚不清楚且存在争议。志贺毒素和其他细胞毒素常被牵连其中，但它们对神经元细胞的作用尚未确定。我们在体外研究了纯化的志贺毒素和从有神经症状儿童分离出的志贺菌超声裂解物对特征明确的人神经母细胞瘤细胞的影响。定量测定显示志贺毒素对HeLa细胞具有高细胞毒性（1.2×10⁶ CD50/毫克纯化毒素），但对LA-N-1、LA-N-5和IMR神经母细胞瘤细胞系没有影响。用肿瘤坏死因子预处理可增加内皮细胞中志贺毒素受体球三糖基神经酰胺的表达并增强志贺毒素的细胞毒性，但不影响神经母细胞瘤细胞对毒素的敏感性。从有神经症状儿童分离出的志贺菌超声裂解物的低稀释度（高达1:16 - 1:64）可导致神经母细胞瘤细胞凝集，但在形态学上未观察到细胞杀伤。这项研究表明，志贺毒素在所检测的人神经母细胞瘤细胞系上不表现出细胞毒性活性，相关志贺菌菌株的超声裂解物也不表现出细胞毒性活性。神经母细胞瘤细胞凝集活性的机制和意义应进一步研究。
