Pilot Projects

试点项目部分包括两个试点项目实例。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中的血清淀粉样蛋白A蛋白水平作为急性期蛋白反应。急性时相蛋白的产生对暴露于人巨噬细胞的致死因子的响应是未知的。血清淀粉样蛋白A是肝外急性时相蛋白之一。研究者将分析培养的人肺泡巨噬细胞中血清淀粉样蛋白A合成的跨国水平和蛋白质合成水平。将这些水平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。研究人员计划确定血清淀粉样蛋白A的生产和降解率在巨噬细胞抵抗致命毒素和敏感致命毒素。最后，研究人员计划将这些研究扩展到人肺模型，并在该肺模型中测定对致死因子治疗的反应中淀粉样纤维和其他急性期蛋白的存在。试验项目2的目标是测试利用抗原特异性分泌抗体预防和治疗B的可行性。炭疽病在人类中的传播建议开发高亲和力的人dIgA， 抗炭疽杆菌Bcl A、PA、LF和EF抗原的抗体，并开发使用 分泌型B抗体。在炭疽的体外和体内模型中预防和治疗炭疽。

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.