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细胞外囊泡与肾内皮细胞:溶血尿毒综合征中的致命吸引

Extracellular Vesicles and Renal Endothelial Cells: A Fatal Attraction in Hemolytic Uremic Syndrome.

机构信息

Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Bologna, Italy.

Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Bologna, Italy.

出版信息

Am J Pathol. 2021 May;191(5):795-804. doi: 10.1016/j.ajpath.2021.02.011. Epub 2021 Feb 27.

Abstract

This review focuses on typical hemolytic uremic syndrome (HUS), a life-threatening sequela of human infections caused, particularly in children, by Shiga toxin-producing Escherichia coli strains. Thrombotic microangiopathy of the brain and the kidney is the end point of toxin action, resulting in the hallmarks of HUS (ie, thrombocytopenia, anemia, and acute renal failure). A growing body of evidence points to the role of extracellular vesicles released in the blood of patients by toxin-challenged circulating cells (monocytes, neutrophils, and erythrocytes) and platelets, as a key factor in the pathogenesis of HUS. This review provides i) an updated description of the pathogenesis of Shiga toxin-producing E. coli infections; ii) an analysis of blood cell-derived extracellular vesicles, and of their parent cells, as triggering factors in HUS; and iii) a model explaining why Shiga toxin-containing vesicles dock preferentially to the endothelia of target organs.

摘要

这篇综述聚焦于典型的溶血性尿毒症综合征(HUS),这是由产志贺毒素大肠杆菌菌株引起的人类感染的一种危及生命的后遗症,尤其在儿童中更为常见。脑和肾脏的血栓性微血管病是毒素作用的终点,导致 HUS 的特征性表现(即血小板减少症、贫血和急性肾衰竭)。越来越多的证据表明,由受到毒素挑战的循环细胞(单核细胞、中性粒细胞和红细胞)和血小板在患者血液中释放的细胞外囊泡,是 HUS 发病机制中的一个关键因素。本综述提供了:i)产志贺毒素大肠杆菌感染发病机制的最新描述;ii)对血细胞衍生的细胞外囊泡及其亲本细胞作为 HUS 触发因素的分析;iii)解释为什么含有志贺毒素的囊泡优先与靶器官的内皮结合的模型。

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