CANDIDA ADHERENCE AND PENETRATION OF VASCULAR ENDOTHELIUM

念珠菌对血管内皮的粘附和穿透

• 批准号: 8174530
• 负责人: John E Edwards
• 金额: $ 0.46万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8174530
• 关键词: Adherence; Antifungal Agents; Candida; Candida albicans; Computer Retrieval of Information on Scientific Projects Database; Defense Mechanisms; Disseminated candidiasis; Endothelial Cells; Endothelium; Funding; Grant; Host Defense Mechanism; Human; Immunomodulators; In Vitro; Infection; Inflammatory Response; Institution; Investigation; Laboratories; Lead; Mediating; Molecular; Organism; Penetration; Play; Proteins; Research; Research Personnel; Resources; Role; Site; Source; Therapeutic; United States National Institutes of Health; Up-Regulation; Vascular Endothelial Cell; Vascular Endothelium; Virulence Factors; attributable mortality; candidemia; in vivo; killings; microbicide; neutrophil; novel strategies; prevent; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. While potent antifungal agents exist that are microbicidal for Candida, the attributable mortality of candidemia is approximately 38%, even with treatment. Many laboratories have shown that endothelial cells play a major role in modifying the inflammatory response. Investigating the interactions of Candida with vascular endothelium has the potential to lead to novel strategies to use endothelial cells to enhance host defense mechanisms. We propose to extend our previous investigations on the molecular mechanisms of the adherence of Candida to endothelial cells, and on the defense mechanisms by which endothelial cells resist damage and invasion by this organism in vitro and in vivo. These studies are aimed at exploring the hypothesis that 1) blocking the adherence of Candida to endothelial cells will prevent their egress from the intravascular compartment, and 2) endothelial cels have mechanisms to resist damage by Candida. These mechanisms are targets to explore for therapeutic up-regulation. These two hypothesis will be evaluated by pursuit of the following specific aims: To determine the role of the ALS1 gene product in mediating the adherence of Candida albicans to human vascular endothelial cells. To determine the mechanisms by which endothelial cells escape damage when C. Albicans is killed by neutrophils on endothelium. To determine whether the immunomodulators and candidal virulence factors identified in our in vitro experiments are expressed at sites of candidal infection in humans with hematogenously disseminated candidiasis.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 虽然存在对念珠菌具有杀菌作用的强效抗真菌剂，但即使经过治疗，念珠菌血症的死亡率约为 38%。许多实验室已经证明内皮细胞在改变炎症反应中发挥着重要作用。研究念珠菌与血管内皮的相互作用有可能产生利用内皮细胞增强宿主防御机制的新策略。 我们建议扩展我们之前对念珠菌粘附内皮细胞的分子机制，以及内皮细胞在体外和体内抵抗该生物体损伤和侵袭的防御机制的研究。这些研究旨在探索以下假设：1）阻断念珠菌与内皮细胞的粘附将阻止其从血管内隔室逸出，2）内皮细胞具有抵抗念珠菌损伤的机制。这些机制是探索治疗上调的目标。这两个假设将通过追求以下具体目标进行评估： 确定 ALS1 基因产物在介导白色念珠菌与人血管内皮细胞粘附中的作用。确定当白色念珠菌被内皮上的中性粒细胞杀死时，内皮细胞逃避损伤的机制。确定我们的体外实验中鉴定的免疫调节剂和念珠菌毒力因子是否在患有血行播散性念珠菌病的人类念珠菌感染部位表达。