RECEPTOR-MEDIATED REGULATION OF MACROPHAGE FUNCTION

拟议研究的长期目标是澄清 Fc-Gamma受体(Fc-Gamma R)在细胞周期调控中的作用 参与免疫反应的细胞的功能。在……里面 这项建议，努力将重点放在生化和 表面存在的Fc-伽马射线的生物学性质 小鼠巨噬细胞表面，由于巨噬细胞的许多功能， 如吞噬调理颗粒，杀死肿瘤细胞， 抗原的呈递，以及分泌的因子 调节T和B细胞，已被证明需要 细胞表面FcγRs的参与。具体目标有：1) 探讨Fc-γ-2AR介导的脑缺血再灌注损伤机制(S) 腺苷酸环化酶的激活；2)进一步鉴定 Fc-Gamma 2b R蛋白的生化性质；3) 研究Fc Gamma 2b R之间的函数关系 和膜上腺苷环化酶系统；以及4)研究 Fc-γR介导的干扰素抑制机制(S) 伽马动作。这些目标将通过以下方式实现：1)生化 日本血吸虫Fc-Gamma R蛋白的特性研究 P388D1，细胞洗涤剂裂解物；2)生产和 定向多克隆抗体和单抗的鉴定 针对分离的Fc-Gamma R蛋白；3)澄清 与IgG2a结合相关的蛋白激酶活性的性质 蛋白质；4)FcGamma 2BR之间关系的描绘 和膜腺苷环化酶；以及5)表征 可能起重要作用的cAMP依赖的蛋白激酶 在干扰素-伽马作用的调制中。获得的结果如下 希望有助于我们对信号通路的理解 透射率，最初由Fc伽马受体在 巨噬细胞表面。还预计拟议的研究将 将为我们提供信息，有助于理解 在初始信号之后的生化事件序列 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.