DYNAMIC PLATELET - STAPHYLOCOCCAL INTERACTIONS

动态血小板 - 葡萄球菌相互作用

• 批准号: 6527722
• 负责人: JULIA M ROSS
• 金额: $ 24.53万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527722
• 关键词: Staphylococcus aureus; bacteria infection mechanism; binding proteins; cardiovascular infection; electron microscopy; erythrocytes; fibrinogen; fibronectins; flow cytometry; host organism interaction; human tissue; integrins; leukocyte activation /transformation; leukocyte adhesion molecules; molecular dynamics; monoclonal antibody; platelet aggregation; platelets; selectins; thrombosis; thrombospondins; tissue /cell culture; vitronectin; von Willebrand factor

DESCRIPTION (Verbatim from Applicant's Abstract): The broad objective of the proposed research is to comprehensively characterize the molecular interactions between Staphylococcus aureus and platelets as a function of the dynamic shear environment in order to provide a rational basis for the development of novel treatments to combat staphylococcal cardiovascular infections. The hypothesis to be tested is that shear stress affects the adhesive interactions between platelets and S. aureus by modulating the (i) relative importance of the adhesive molecules involved and (ii) the reaction binding kinetics. The proposed approach uses controlled, dynamic, in vitro experimental systems to systematically and comprehensively examine the importance of platelet activation, blood components, blood flow, and bacteria in the development of blood-born staphylococcal infections. A long-term goal of this work is to investigate the interrelationship between thrombogenesis and cardiovascular infection mechanisms. The specific aims of the project are to: 1) comprehensively elucidate the molecular mechanisms of S. aureus-platelet interactions under shear conditions of direct physiological relevance; 2) characterize S. aureus-platelet heteroaggregation in cell suspensions subjected to controlled levels of shear and; 3) develop a protocol to study S. aureus-platelet aggregation in whole blood and to evaluate the effect of this extension on S. aureus-platelet interactions under shear conditions. Completion of these specific aims will provide a rational basis for the design of new therapeutic molecules to block specific adhesion events, as well as identify the most important bacterial receptors to target in vaccine development.

描述（逐字摘自申请人摘要）：本研究的总体目标