Tissue factor–dependent procoagulant activity of subtilase cytotoxin, a potent AB5 toxin produced by shiga toxigenic Escherichia coli.
Tissue factor–dependent procoagulant activity of subtilase cytotoxin, a potent AB5 toxin produced by shiga toxigenic Escherichia coli.
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枯草杆菌酶细胞毒素的组织因子依赖性促凝血活性，枯草杆菌酶细胞毒素是由产志贺毒素大肠杆菌产生的强效 AB5 毒素。
DOI：
10.1086/656534
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Paton,AdrienneW
中科院分区：
文献类型：
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作者：
Wang,Hui;Paton,JamesC;Thorpe,ChelesteM;Bonder,ClaudineS;Sun,WaiYan;Paton,AdrienneW
枯草杆菌细胞毒素(SubAB)是由致病性志贺毒素大肠杆菌产生的，可引起小鼠溶血性尿毒症综合征样病理，包括广泛的微血管血栓形成。SubAB通过特异性地切割必需的内质网伴侣结合免疫球蛋白(Bip)来发挥作用。据报道，BiP可以抑制组织因子(TF)的激活，组织因子是外源性凝血的主要启动者。我们推测，SubAB在体内的明显促血栓形成作用可能涉及刺激依赖于Tf的促凝血活性。因此，在暴露于SubAB的人巨噬细胞和原代人脐静脉内皮细胞中，检测了依赖于TF的促凝血活性、TF信使RNA(MRNA)水平和Bip裂解。在这两种类型的细胞中，SubAB显著增加TF依赖的促凝活性，诱导TF mRNA的表达，并介导Bip的切割。当细胞被一种非蛋白水解性突变毒素SubAA272B处理时，没有看到任何影响。我们的结果表明，SubAB的促凝作用可能依赖于TF表达的上调和通过Bip裂解激活TF。
Subtilase cytotoxin (SubAB), produced by certain virulent Shiga toxigenicEscherichia colistrains, causes hemolytic uremic syndrome-like pathology in mice, including extensive microvascular thrombosis. SubAB acts by specifically cleaving the essential endoplasmic reticulum chaperone binding immunoglobulin protein (BiP). BiP has been reported to inhibit the activation of tissue factor (TF), the major initiator of extrinsic coagulation. We hypothesized that the apparent prothrombotic effect of SubAB in vivo may involve the stimulation of TF-dependent procoagulant activity. TF-dependent procoagulant activity, TF messenger RNA (mRNA) levels, and BiP cleavage were therefore examined in human macrophage cells and primary human umbilical vein endothelial cells exposed to SubAB. In both types of cells, SubAB significantly increased TF-dependent procoagulant activity, induced TF mRNA expression, and mediated BiP cleavage. No effects were seen when cells were treated with a nonproteolytic mutant toxin, SubAA272B. Our results suggest that the procoagulant effect of SubAB may be dependent on both the up-regulation of TF expression and the activation of TF by means of BiP cleavage.