Translocation of Shiga toxin across polarized Intestinal cells in tissue culture
Translocation of Shiga toxin across polarized Intestinal cells in tissue culture
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DOI：
10.1128/iai.64.8.3294-3300.1996
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发表时间：
1996-08-01
影响因子：
3.1
通讯作者：
Keusch, GT
中科院分区：
文献类型：
--
作者：
Acheson, DWK;Moore, R;Keusch, GT
产生滋贺毒素（Stx）1和2的大肠杆菌菌株定殖于人类的下胃肠道并且与胃肠道和全身性疾病相关。在感染患者的粪便中可检测到Stx，并且很可能毒素从肠道腔传递到下面的组织。本研究的目的是开发体外模型以研究Stx穿过完整的极化细胞单层。在聚碳酸酯过滤器上生长的四种细胞系中检查了生物活性Str的易位。Stx 1以能量需求和饱和的方式跨肠细胞单层（CaCo 2A和T84细胞）易位，而单层保持高水平的电阻。Stx 1对这些细胞系的电阻或菊粉运动没有影响，至少24小时。丁酸钠诱导特异性Stx受体降低了CaCo 2A单层转运的毒素比例，但对辣根过氧化物酶或[H-3]菊粉的运动没有重大影响。我们已经表明，生物活性的Stx 1能够穿过完整的极化肠上皮细胞，而没有明显的细胞破坏，可能是通过跨细胞途径。数据还表明，在肠上皮细胞的顶端表面上的Stx受体的存在可以提供一些保护，防止管腔Stx 1的吸收。
Escherichia coli strains producing Shiga toxins (Stx) 1 and 2 colonize the lower gastrointestinal tract in humans and are associated with gastrointestinal and systemic diseases. Stx are detectable in the feces of infected patients, and it is likely that toxin passes from the intestinal tract lumen to underlying tissues, The objective of this study was to develop an in vitro model to study the passage of Stx across intact, polarized cell monolayers. Translocation of biologically active Str was examined in four cell lines grown on polycarbonate filters. Stx1 translocated across intestinal cell monolayers (CaCo2A and T84 cells) in an energy-requiring and saturable manner, while the monolayers maintained a high level of electrical resistance. Stx1 had no effect on electrical resistance or inulin movement across these cell lines for at least 24 h. Induction of specific Stx receptors with sodium butyrate reduced the proportion of toxin translocated across CaCo2A monolayers but had no major effect on the movement of horseradish peroxidase or [H-3]inulin. We have shown that biologically active Stx1 is capable of moving across intact polarized intestinal epithelial cells without apparent cellular disruption, probably via a transcellular pathway, The data also suggest that the presence of Stx receptors on the apical surface of intestinal epithelial cells mag offer some protection against the absorption of luminal Stx1.