RECEPTOR-MEDIATED REGULATION OF MACROPHAGE FUNCTIONS

我们的长期目标是清楚地描绘生物化学途径 由配体和特定细胞之间的相互作用触发 并导致巨噬细胞功能调节。我们将 将我们的努力集中在Fc-γ的生物化学和生物学特性上， Rs存在于小鼠巨噬细胞表面，因为许多巨噬细胞 功能，如吞噬调理颗粒，杀死肿瘤 细胞、抗原呈递和调节T细胞的因子分泌 和B细胞，已经证明需要细胞表面的参与 Fc-γ-Rs。具体目的是调查：1）生理作用， 与Fc-γ（2a）R相关的酪蛋白激酶II（CKII）活性; 2） Fc-γ（2a）R的生物化学和分子生物学特性 方法; 3）G蛋白在磷脂酶调节中的作用 C和A2由免疫复合物或LPS激活;和4） cAMP依赖性蛋白激酶（cAK）和蛋白激酶C（PKC）在 调节巨噬细胞功能。我们将努力实现这些具体目标 通过：1）Fc-γ（2a）R复合物的生物化学表征; 2）Fc-γ（2a）R复合物的克隆， 通过消减杂交方法编码Fc-γ（2a）R的基因; 3） Fc-γ（2a）R相关CKII活性的表征; 4） 吞噬作用期间Fc-γ-R-细胞骨架相互作用的研究; 5)比较巨噬细胞系中G蛋白的性质;以及 6)cAK和PKC的表征。预计取得的成果将 促进我们对信号的生化途径的理解 透射率，其最初由细胞表面FC-γ-R触发， 调节巨噬细胞的功能

Our long-term objectives are to clearly delineate the biochemical pathways which are triggered by the interaction between ligand and specific cell surface receptor and lead to modulation of macrophage functions. We will focus our efforts on the biochemical and biological properties of Fc-gamma- Rs present on the surface of murine macrophage, because many of macrophage functions, such as phagocytosis of opsonized particles, killing of tumor cells, presentation of antigens, and secretion of factors which regulate T and B cells, have been shown to require the participation of cell surface Fc-gamma-Rs. Specific aims are to investigate: 1) physiological roles of casein kinase II (CKII) activity associated with Fc-gamma(2a)R; 2) properties of Fc-gamma(2a)R by biochemical and molecular biological approaches; 3) the roles of G proteins in the regulation of phospholipases C and A2 activated by immune complex or LPS; and 4) the role of cAMP-dependent protein kinase (cAK) and protein kinase C (PKC) in the regulation of macrophage functions. We will approach to these specific aims by: 1) biochemical characterization of Fc-gamma(2a)R complex; 2) cloning of the gene coding for Fc-gamma(2a)R by subtractive hybridization method; 3) characterization of Fc-gamma(2a)R-associated CKII activity; 4) investigation of Fc-gamma-R-cytoskeletal interaction during phagocytosis; 5) comparison of the nature of G proteins among macrophage cell lines; and 6) characterization of cAK and PKC. Results obtained are expected to promote our understanding of the biochemical pathways of signal transmittance, which are initially triggered by cell surface FC-gamma-R and leads to the regulation of macrophage functions.