Anthrax toxin entry into polarized epithelial cells
Anthrax toxin entry into polarized epithelial cells
复制标题
DOI：
10.1128/iai.67.6.3026-3030.1999
复制
发表时间：
1999-06-01
影响因子：
3.1
通讯作者：
Lencer, WI
中科院分区：
文献类型：
--
作者：
Beauregard, KE;Wimer-Mackin, S;Lencer, WI
我们研究了炭疽水肿毒素（EdTx）进入极化的人T84上皮细胞使用环AMP调节的Cl-分泌作为毒素进入的指标。EdTx是一种二元A/B毒素，其在细胞表面由炭疽水肿因子和保护性抗原（PA）自组装。PA与细胞表面受体结合，并将EF（一种腺苷酸环化酶）递送至胞质溶胶。EdTx引起强烈的Cl-分泌反应时，它被施加到T84细胞的基底外侧表面，但没有响应时，它被施加到顶端表面。单独使用PA没有效果：当它应用于任何表面时。暴露于基底外侧的T84细胞与PA的结合比暴露于顶部的T84细胞多至少30倍，这表明PA受体在很大程度上或完全局限于这些细胞的基底外侧膜。PA受体不像霍乱毒素受体那样与不溶于洗涤剂的小窝样膜破裂。这些发现对PA受体的性质有影响，并证实了EdTx和CT从根本上选择不同的亚细胞系统进入细胞并引起疾病的观点。
We examined the entry of anthrax edema toxin (EdTx) into polarized human T84 epithelial cells using cyclic AMP-regulated Cl- secretion as an index of toxin entry. EdTx is a binary A/B toxin which self assembles at the cell surface from anthrax edema factor and protective antigen (PA). PA binds to cell surface receptors and delivers EF, an adenylate cyclase, to the cytosol. EdTx elicited a strong Cl- secretory response when it was applied to the basolateral surface of T84 cells but no response when it was applied to the apical surface. PA alone had no effect: when it was applied to either surface. T84 cells exposed basolaterally bound at least 30-fold-more PA than did T84 cells exposed apically, indicating that the PA receptor is largely or completely restricted to the basolateral membrane of these cells. The PA receptor did not fractionate with detergent-insoluble caveola-like membranes as cholera toxin receptors do. These findings have implications regarding the nature of the PA receptor and confirm the view that EdTx and CT coopt fundamentally different subcellular systems to enter the cell and cause disease.