RECEPTOR-MEDIATED REGULATION OF MACROPHAGE FUNCTION

拟议研究的长期目标是阐明 Fc γ受体（Fc γ R）在调节 参与免疫反应的细胞的功能。 在 这项建议，努力将集中在生物化学和 存在于表面上的Fc γ R的生物学性质 鼠巨噬细胞表面，由于许多巨噬细胞的功能， 例如吞噬调理颗粒，杀死肿瘤细胞， 抗原的呈递和分泌因子， 调节T和B细胞，已经证明需要 细胞表面Fc γ R的参与。 具体目标是：1） 研究Fc γ 2aR介导的免疫抑制机制， 腺苷酸环化酶的活化; 2）进一步表征 Fc γ 2b R蛋白的生物化学性质; 3） 研究Fc γ 2b R 和膜腺苷酸环化酶系统;和4）调查 Fc γ R介导的IFN抑制机制 伽马作用 这些目标将通过以下方式实现：1）生物化学 分离的Fc γ R蛋白的表征 P388 D1细胞的去污剂裂解物; 2）生产和 多克隆和单克隆抗体的鉴定 针对分离的Fc γ R蛋白; 3）澄清 与IgG 2a结合相关的蛋白激酶活性的性质 蛋白质; 4）描绘Fc γ 2bR 和膜腺苷酸环化酶;和5）表征 cAMP依赖性蛋白激酶，可能发挥重要作用 干扰素γ的调节作用。 结果令人 希望能帮助我们理解 透射率，最初由Fc γ受体触发， 巨噬细胞表面 预计拟议的研究还将 会给我们提供信息，有助于理解 事件的生化序列，遵循初始信号 并导致巨噬细胞功能的调节。

Long-term objective of the proposed research is to elucidate the roles of Fc gamma receptors (Fc gamma R) in the regulation of functions of cells which participate in the immune response. In this proposal, efforts will be focused on the biochemical and biological properties of Fc gamma Rs present on the surface of murine macrophage surface, since many of macrophage functions, such as phagocytosis of opsonized particles, killing of tumor cells, presentation of antigens, and the secretion of factors which modulate T and B cells, have been shown to require the participation of cell surface Fc gamma Rs. Specific aims are: 1) to investigate the Fc gamma 2aR-mediated mechanism(s) of the activation of adenylate cyclase; 2) to further characterize the biochemical properties of Fc gamma 2b R protein; 3) to investigate the functional relationship between Fc gamma 2b R and the membrane adenylate cyclase system; and 4) to investigate the Fc gamma R-mediated mechanism(s) of the suppression of IFN gamma action. These aims will be approached by: 1) biochemical characterization of Fc gamma R proteins isolated from the detergent lysate of P388D1, cells; 2) production and characterization of polyclonal and monclonal antibodies directed against the isolated Fc gamma R proteins; 3) clarification of the nature of protein kinase activities associated with IgG2a-binding proteins; 4) delineation of the relationship between Fcgamma 2bR and membrane adenylate cyclase; and 5) characterization of cAMP-dependent protein kinases which may play an essential role in the modulation of the IFN gamma action. Results obtained are expected to aid our understanding of the pathways of signal transmittance, initially triggered by Fc gamma receptors at the macrophage surface. It is also expected that the proposed studies will give us informations, useful for the understanding of the biochemical sequence of events, which follows the initial signal and leads to the regulation of macrophage function.