RECEPTOR-MEDIATED REGULATION OF MACROPHAGE FUNCTIONS

我们的长期目标是清楚地描绘出生化途径 它是由配体和特定细胞之间的相互作用触发的 表面受体并导致巨噬细胞功能的调节。我们会 将我们的精力集中在FC-伽马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 吞噬调理颗粒、杀灭肿瘤等功能 细胞、抗原的呈递和调节T细胞的因子的分泌 和B细胞，已被证明需要细胞表面的参与 Fc-Gamma-Rs。具体目的是调查：1)生理作用 酪蛋白激酶II(CKII)活性与Fc-γ(2a)R；2 Fc-γ(2a)R的生化和分子生物学性质 方法：3)G蛋白在磷脂酶调节中的作用 C和A2由免疫复合体或内毒素激活；以及4) 细胞内cAMP依赖的蛋白激酶(CAK)和蛋白激酶C(PKC) 巨噬细胞功能的调节。我们将实现这些具体目标 通过：1)Fc-γ(2a)R复合体的生化特性；2)克隆 应用消减杂交法获得Fc-γ(2a)R基因编码序列； Fc-γ(2a)R相关CKII活性的表征；4) 吞噬过程中Fc-γ-R与细胞骨架相互作用的研究 5)巨噬细胞系之间G蛋白性质的比较； 6)CAK和PKC的特征。预计所取得的结果将 促进我们对信号的生化途径的理解 透过率，最初由细胞表面Fc-Gamma-R和 导致巨噬细胞功能的调节。

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.