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）：Bartonella henselae细菌 引起多种疾病综合征，包括严重的全身性 艾滋病患者威胁生命的感染。 NIH与HIV相关的计划 研究（FY2002）列出了目标2F作为“阐明的致病机制 成人和儿童的艾滋病毒相关机会感染。 识别Henselae作为一种新兴病原体，对 这种细菌引起疾病的新型机制。这个项目 靶向Bartonella发病机理（血管生成）最独特的方面，即 主要观察到杆菌血管瘤病（BA）和 芽孢杆菌肝肝（BPH）。该提议的核心假设是 基于henselae诱导的血管生成的新模型，我们已经采用了 需要在表面蛋白和Henselae的结构中起主要作用 这个过程。提出了以下具体目的来检验假设： 1）确定henselae的四个主要表面结构中的每一个 与宿主内皮细胞相互作用，2）检查B的能力。 Henselae和Henselae的四个主要表面结构中的每个 血管内皮生长因子（VEGF）的产生，3）确定是否VEGF 通过B. henselae与其他细胞类型的相互作用产生的能力 以旁分泌的方式功能诱导人类微丝虫的增殖 内皮细胞。体外细胞培养系统将用于两者 诱导VEGF（巨噬细胞，成纤维细胞！上皮细胞）以及 内皮细胞的增殖导致血管生成。定义 B. henselae使用的致病过程将帮助我们更好地理解 为什么这种细菌在健康个体和严重的人中引起轻度疾病 艾滋病患者中的疾病在内，包括BA和BPH。