原代人结肠上皮细胞（pHCoEpiCs）确实表达志贺毒素（Stx）受体糖鞘脂Gb3Cer 和 Gb4Cer，对 Stx 主要表现为不易感，但并非耐药。

Primary Human Colon Epithelial Cells (pHCoEpiCs) Do Express the Shiga Toxin (Stx) Receptor Glycosphingolipids Gb3Cer and Gb4Cer and Are Largely Refractory but Not Resistant towards Stx.

机构信息

Institute for Hygiene, University of Münster, 48149 Münster, Germany.

Institute for Food Chemistry, University of Münster, 48149 Münster, Germany.

出版信息

Int J Mol Sci. 2021 Sep 16;22(18):10002. doi: 10.3390/ijms221810002.

DOI:10.3390/ijms221810002

PMID:34576167

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8472147/

Abstract

Shiga toxin (Stx) is released by enterohemorrhagic (EHEC) into the human intestinal lumen and transferred across the colon epithelium to the circulation. Stx-mediated damage of human kidney and brain endothelial cells and renal epithelial cells is a renowned feature, while the sensitivity of the human colon epithelium towards Stx and the decoration with the Stx receptor glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer, Galα1-4Galβ1-4Glcβ1-1Cer) and globotetraosylceramide (Gb4Cer, GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1Cer) is a matter of debate. Structural analysis of the globo-series GSLs of serum-free cultivated primary human colon epithelial cells (pHCoEpiCs) revealed Gb4Cer as the major neutral GSL with Cer (d18:1, C16:0), Cer (d18:1, C22:1/C22:0) and Cer (d18:1, C24:2/C24:1) accompanied by minor Gb3Cer with Cer (d18:1, C16:0) and Cer (d18:1, C24:1) as the dominant lipoforms. Gb3Cer and Gb4Cer co-distributed with cholesterol and sphingomyelin to detergent-resistant membranes (DRMs) used as microdomain analogs. Exposure to increasing Stx concentrations indicated only a slight cell-damaging effect at the highest toxin concentration of 1 µg/mL for Stx1a and Stx2a, whereas a significant effect was detected for Stx2e. Considerable Stx refractiveness of pHCoEpiCs that correlated with the rather low cellular content of the high-affinity Stx-receptor Gb3Cer renders the human colon epithelium questionable as a major target of Stx1a and Stx2a.

摘要

志贺毒素（Stx）由肠出血性（EHEC）释放到人类肠道腔中，并穿过结肠上皮转移到循环系统。Stx 介导的人肾和脑内皮细胞以及肾上皮细胞的损伤是一个众所周知的特征，而人结肠上皮对 Stx 的敏感性以及 Stx 受体糖鞘脂（GSLs）神经节苷脂 Gb3Cer（Galα1-4Galβ1-4Glcβ1-1Cer）和神经节苷脂 Gb4Cer（GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1Cer）的装饰是有争议的。无血清培养的原代人结肠上皮细胞（pHCoEpiCs）的 globo 系列 GSL 的结构分析表明，Gb4Cer 是主要的中性 GSL，带有 Cer（d18:1，C16:0）、Cer（d18:1，C22:1/C22:0）和 Cer（d18:1，C24:2/C24:1），同时还有少量的 Gb3Cer，带有 Cer（d18:1，C16:0）和 Cer（d18:1，C24:1）作为主要的脂类形式。Gb3Cer 和 Gb4Cer 与胆固醇和神经鞘磷脂一起分布在去污剂抗性膜（DRMs）中，DRMs 被用作微区模拟物。随着 Stx 浓度的增加，只有在 Stx1a 和 Stx2a 的最高毒素浓度 1μg/mL 时，细胞才会受到轻微的损伤，而 Stx2e 则会产生明显的作用。pHCoEpiCs 对 Stx 的抵抗力相当大，这与高亲和力 Stx 受体 Gb3Cer 的细胞含量较低有关，这使得人结肠上皮细胞成为 Stx1a 和 Stx2a 的主要靶标受到质疑。