Pilot Projects

试点项目组成部分包括两个试点项目示例。在试点项目1中，研究人员建议研究暴露于炭疽致死毒素的人肺泡巨噬细胞的血清淀粉样蛋白A水平作为急性期蛋白反应。急性期蛋白的产生是对暴露于人巨噬细胞致死因子的反应尚不清楚。肝外急性期蛋白之一是血清淀粉样蛋白A。研究人员将分析培养的人肺泡巨噬细胞中血清淀粉样蛋白A的跨国合成水平和蛋白质合成水平。这些水平将与暴露于其他细菌挑战（如细菌LPS）的人肺泡巨噬细胞进行比较。研究人员计划测定巨噬细胞中对致命毒素有抗性和对致命毒素敏感的血清淀粉样蛋白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类肺模型，并在该肺模型中检测淀粉样蛋白原纤维和其他急性期蛋白对致死因子治疗的反应。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炭疽杆菌感染的可行性。提出了开发高亲和度的人类dIgA的设想

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.