Bartonella henselae antigens of biological significance

描述(申请人提供)：亨氏巴尔通氏菌 导致各种疾病症状，包括严重的系统性 艾滋病患者中危及生命的感染。美国国立卫生研究院艾滋病毒相关计划 研究(2002财年)将目标2F列为“阐明致病机制 成人和儿童中艾滋病毒相关的机会性感染。 识别亨氏假单胞菌为一种新的病原体，目前知之甚少 这种细菌致病的新机制。这个项目 针对巴尔通体致病最独特的方面(血管生成)，即 主要见于患有杆状血管瘤病(BA)的艾滋病患者和 细菌性肝炎(BPH)。这项提议的中心假设是 基于我们提出的一种新的亨氏杆菌诱导的血管生成模型 要求亨氏假单胞菌表面蛋白和结构在 这一过程。为了检验这一假设，我们提出了以下具体目标： 1)确定亨氏假单胞菌四种主要表面结构各自的作用 发挥与宿主内皮细胞的相互作用，2)检测B。 以及亨塞莱斯的四种主要表面结构中的每一种都能诱导 血管内皮生长因子的产生，3)决定血管内皮生长因子是否 由亨塞氏杆菌与其他细胞类型相互作用产生的 以旁分泌方式诱导人微血管的增殖 内皮细胞。体外细胞培养系统将用于两种 诱导血管内皮生长因子(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。概念的定义 亨氏杆菌的致病过程将有助于我们更好地了解 为什么这种细菌会在健康的人中引起轻微的疾病，而严重的 艾滋病患者的疾病包括BA和BPH。

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.