Bartonella henselae antigens of biological significance

具有生物学意义的汉赛巴尔通体抗原

• 批准号: 6627792
• 负责人: BURT E ANDERSON
• 金额: $ 32.63万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627792
• 关键词: HIV infections; Rickettsiales; Rickettsiales disease; angiogenesis; bacteria infection mechanism; bacterial antigens; blood vessel disorder; cell proliferation; emerging infectious disease; genetic library; human tissue; opportunistic infections; paracrine; tissue /cell culture; vascular endothelial growth factors

DESCRIPTION (Provided by the applicant): The bacterium Bartonella henselae causes a variety of disease syndromes including severe systemic life-threatening infections in AIDS patients. The NIH Plan for HIV-Related Research (FY2002) lists objective 2F as "elucidate the pathogenic mechanism of HIV-related opportunistic infections in adults and children." Despite the recognition of B. henselae as an emerging pathogen, very little is known about the novel mechanisms by which this bacterium causes disease. This project targets the most unique aspect of Bartonella pathogenesis (angiogenesis), that is observed primarily in AIDS patients with bacillary angiomatosis (BA) and bacillary peliosis hepatis (BPH). The central hypothesis of this proposal is based on a new model of B. henselae -induced angiogenesis that we have advanced requiring a major role for surface proteins and structures of B. henselae in this process. The following specific aims are proposed to test the hypothesis: 1) determine the role each of the four major surface structures of B. henselae play in interaction with host endothelial cells, 2) examine the ability of B. henselae and each of the four major surface structures of B. henselae to induce production of vascular endothelial growth factor (VEGF), 3) determine if VEGF produced by interaction of B. henselae with other cell types is able to function in a paracrine manner to induce proliferation of human microvascula endothelial cells. In vitro cell culture systems will be utilized for both the induction of VEGF (macrophages, fibroblast! epithelial cells) as well as the proliferation of endothelial cells leading to angiogenesis. The definition of the pathogenic processes utilized by B. henselae will help us better understand why this bacterium causes a mild disease in healthy individuals and severe diseases including BA and BPH in AIDS patients.

描述（由申请人提供）：细菌汉赛巴尔通体 引起多种疾病综合症，包括严重的全身性疾病 危及艾滋病患者生命的感染。 NIH 艾滋病毒相关计划 研究（2002 财年）将目标 2F 列为“阐明疾病的致病机制” 成人和儿童中与艾滋病毒相关的机会性感染。” 汉赛芽孢杆菌被认为是一种新兴病原体，但人们对此知之甚少 这种细菌引起疾病的新机制。这个项目 针对巴尔通体发病机制（血管生成）最独特的方面， 主要在患有细菌性血管瘤病 (BA) 的 AIDS 患者中观察到 杆菌性紫癜性肝炎 (BPH)。该提案的中心假设是 基于我们提出的 B. henselae 诱导血管生成的新模型 需要 B. henselae 的表面蛋白和结构发挥重要作用 这个过程。提出以下具体目标来检验假设： 1) 确定 B. henselae 四种主要表面结构各自的作用 与宿主内皮细胞相互作用，2) 检查 B. henselae 和 B. henselae 的四个主要表面结构中的每一个都诱导 血管内皮生长因子 (VEGF) 的产生，3) 确定 VEGF 是否 B. henselae 与其他细胞类型相互作用产生的能够 以旁分泌方式发挥作用，诱导人体微血管增殖 内皮细胞。体外细胞培养系统将用于 VEGF（巨噬细胞、成纤维细胞！上皮细胞）以及 内皮细胞增殖导致血管生成。的定义 B. henselae 利用的致病过程将帮助我们更好地了解 为什么这种细菌会在健康个体中引起轻度疾病，而在健康个体中引起严重疾病 艾滋病患者的疾病包括 BA 和 BPH。