Pilot Projects

试点项目

• 批准号: 6847233
• 负责人: Carol F Webb
• 金额: $ 15.15万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6847233
• 关键词: Bacillus anthracis; acute phase protein; anthrax; anthrax toxin; bactericidal immunity; cooperative study; humoral immunity

The Pilot Project Component includes two examples of pilot projects. In pilot project 1 the investigators propose to study serum amyloid A protein levels in human alveolar macrophages exposed to anthrax lethal toxin as an acute phase protein response. The generation of acute phase proteins in response to the lethal factor exposure to human macrophages is unknown. One of the extrahepatic acute phase proteins is serum amyloid A. The investigators will analyze the level of serum amyloid A synthesis at the transnational and protein synthesis levels in cultured human alveolar macrophages. These levels will be compared with human alveolar macrophages exposed to other bacterial challenge such as bacterial LPS. The investigators plan to determine the serum amyloid A production and degradation rates in macrophages resistant to lethal toxin and sensitive to lethal toxin. Lastly, the investigators plan to extend these studies to the human lung model and assay for the presence for amyloid fibrils and other acute phase proteins in response to treatment with lethal factor in this lung model. The goal of pilot project 2 is to test the feasibility of utilizing antigen specific secretory antibodies for the prevention and treatment of B. anthracis infection in humans. It is proposed to develop high affinity human dIgA antibodies to Bacillus anthracis Bcl A, PA, LF and EF antigens and to develop a means of using secretory antibodies to B. anthracis for prophylaxis and therapy in both in vitro and in vivo models of anthrax.

试点项目部分包括两个试点项目示例。在试点项目 1 中，研究人员提议研究暴露于炭疽致死毒素的人类肺泡巨噬细胞中的血清淀粉样蛋白 A 水平，作为急性期蛋白反应。人类巨噬细胞暴露致死因子后产生急性期蛋白的情况尚不清楚。肝外急性期蛋白之一是血清淀粉样蛋白A。研究人员将在培养的人肺泡巨噬细胞中分析跨国水平和蛋白质合成水平上的血清淀粉样蛋白A合成水平。这些水平将与暴露于其他细菌挑战（例如细菌 LPS）的人类肺泡巨噬细胞进行比较。研究人员计划确定对致命毒素具有抵抗力和对致命毒素敏感的巨噬细胞中血清淀粉样蛋白 A 的产生和降解率。最后，研究人员计划将这些研究扩展到人肺模型，并测定淀粉样原纤维和其他急性期蛋白的存在，以响应该肺模型中致命因子的治疗。试点项目2的目标是测试利用抗原特异性分泌抗体预防和治疗人类炭疽杆菌感染的可行性。拟开发高亲和力人dIgA 炭疽杆菌 Bcl A、PA、LF 和 EF 抗原的抗体，并开发一种使用方法 炭疽芽孢杆菌的分泌抗体，用于炭疽体外和体内模型的预防和治疗。