SHIGA-LIKE TOXIN--ENDOTHELIAL CELL INTERACTIONS

志贺样毒素--内皮细胞相互作用

基本信息

批准号：
2905945
负责人：
TOM G OBRIG
金额：
$ 11.29万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-09-30 至 2001-08-31
项目状态：
已结题

项目摘要

Hemolytic uremic syndrome (HUS) is a vascular disease with primary damage of the kidney in which glomerular microcapillaries become occluded with fibrin and platelets. Although HUS is associated with bacteria, viruses, immunosuppressants and AIDS, little is known about the mechanisms leading to the development of HUS. Most new information on HUS has come from studies related to the E. coli Shiga-like toxin (SLT)-producing dysentery bacteria and the subsequent appearance of HUS in those individuals. Our long-term goal is to describe, in biochemical terms, the mechanisms by which SLTs and host factors elicit the HUS disease state and to use this knowledge to develop effective preventive or therapeutic intervention modalities. The goal of the present study is to delineate the role of SLTs at the vascular endothelial cell level in the development of HUS. These studies utilize the human renal microvascular endothelial cell type which is believed to be the primary target of SLTs during the development of MUS. Our research plan seeks to answer why some endothelial cell types are more sensitive to the SLTs than are others and why human renal endothelial cells are particularly sensitive to SLT-2, as we recently demonstrated. The research plan is designed to examine the interaction of SLTs with endothelial cells under vascular flow conditions. A microchannel flow system is included which more closely represents the geometry, flow rate, and shear stress conditions of the kidney microvasculature where conditions of HUS occur. The contribution of flow parameters will be examined at the endothelial level for SLT binding and for subsequent effects on endothelial physiology. In summary, this research combines the areas of infectious disease and vascular physiology, and has as its primary goal to provide an understanding of the mechanisms underlying the development of renal vascular disease in HUS.

溶血性尿毒症综合征（HUS）是一种血管疾病，主要损害肾小球微毛细血管被阻塞的肾脏纤维蛋白和血小板。尽管HUS与细菌，病毒相关，但免疫抑制剂和艾滋病，对领先的机制知之甚少为了发展Hus。关于HUS的大多数新信息来自与大肠杆菌类毒素（SLT）产生痢疾有关的研究细菌和随后在这些个体中的HUS出现。我们的长期目标是用生化术语来描述通过哪些SLT和寄主因素引起了HUS疾病状态并使用知识以开发有效的预防或治疗干预方式。本研究的目的是描述 HUS发育中血管内皮细胞水平的SLT。这些研究利用人类肾脏微血管内皮细胞类型据信这是开发过程中SLT的主要目标 mus。我们的研究计划试图回答为什么某个内皮细胞类型对SLT的敏感性比其他类型更敏感正如我们最近，内皮细胞对SLT-2特别敏感证明。该研究计划旨在检查互动在血管流条件下具有内皮细胞的SLT。一个包括微通道流系统，更紧密地表示肾脏的几何，流速和剪切应力条件发生HUS条件的微脉管系统。流量的贡献参数将在内皮层进行检查，以进行SLT结合和随后对内皮生理的影响。总而言之，这研究结合了传染病和血管的领域生理学，并具有提供理解的主要目标肾血管疾病发展的基础机制胡斯。