Bartonella henselae antigens of biological significance

性状（由申请方提供）：汉赛巴尔通体 引起多种疾病综合征，包括严重的全身性 艾滋病患者的致命感染。美国国立卫生研究院计划与艾滋病毒有关 研究（2002财政年度）将目标2F列为“阐明 成人和儿童中与艾滋病毒相关的机会性感染。“尽管 识别B。henselae作为一种新出现的病原体，对它知之甚少。 这种细菌致病的新机制这个项目 靶向巴尔通体发病机制（血管生成）的最独特方面， 主要在患有杆菌性血管瘤病（BA）的艾滋病患者中观察到， 细菌性肝炎（BPH）。这一提议的核心假设是 基于B的新模型。亨瑟莱诱导的血管生成 需要表面蛋白和B结构的主要作用。汉瑟莱因 这个过程为检验这一假设，提出了以下具体目标： 1)确定B的四种主要表面结构各自的作用。henselae 与宿主内皮细胞的相互作用; 2）检测B. henselae和B的四种主要表面结构中的每一种。henselae诱导 血管内皮生长因子（VEGF）的产生，3）确定VEGF是否 由B的相互作用产生。henselae与其他细胞类型能够 以旁分泌方式诱导人微血管增殖 内皮细胞体外细胞培养系统将用于这两种情况。 VEGF（巨噬细胞，成纤维细胞！上皮细胞）以及 导致血管生成的内皮细胞增殖。的定义 B利用的致病过程。henselae将帮助我们更好地理解 为什么这种细菌会在健康个体中引起轻度疾病， 包括BA和BPH在内的疾病。

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.