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 dIgAantibodies to Bacillus anthracis Bcl A, PA, LF and EF antigens and to develop a means of usingsecretory antibodies to B. anthracis for prophylaxis and therapy in both in vitro and in vivo models of anthrax.
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