MOLECULAR EVENTS IN NEUTROPHIL PHAGOCYTOSIS BY IGA

人外周血中性粒细胞具有针对血清IgA的Fc受体 免疫球蛋白，但这些受体需要激活才能 功能齐全。我们实验室最近的研究表明，粒细胞- 巨噬细胞集落刺激因子(GM-CSF)增强中性粒细胞IgA- 介导的吞噬作用。这项研究提案的目标是 描述导致中性粒细胞免疫球蛋白A活化的分子事件 通过GM-CSF检测Fc受体。我们的研究将包括生物化学和 中性粒细胞IgA Fc受体激活的生理学研究 中性粒细胞IgA Fc受体的分子特征。这些目标将是 通过以下具体目标来实现：1.制备单抗 抗中性粒细胞IgA Fc受体的单抗。单抗将被用于 研究受体的生物合成，表征受体的结合部位 免疫球蛋白，并评估受体内化、降解或循环。2. 中性粒细胞IgA Fc受体生物学功能的研究 由GM-CSF激活。将进行研究，以建立新的IgA模型- 微球介导GM-CSF的吞噬和ADCC反应 生物体和肿瘤细胞。3.描述生物化学事件的特征 GM-CSF激活中性粒细胞IgA Fc受体。我们将研究这一角色 蛋白质合成，GTP结合蛋白，钙通量的变化， 受体磷酸化、糖基化与受体结构反应 给GM-CSF。我们将确定IgA受体是否内化并 降解的，或回收的。4.克隆编码中性粒细胞IgA Fc的基因(S) 感受器。

Human peripheral blood neutrophils have Fc receptors for serum IgA immunoglobulins, but these receptors require activation before they are functional. Recent studies from our laboratory show that granulocyte- macrophage colony-stimulating factor (GM-CSF) enhances neutrophil IgA- mediated phagocytosis. The goal of this research proposal is to characterize the molecular events leading to activation of neutrophil IgA Fc receptors by GM-CSF. Our studies will encompass the biochemistry and physiology of neutrophil IgA Fc receptor activation, including studies to molecularly characterize neutrophil IgA Fc receptors. These goals will be achieved by the following specific aims to: 1. Produce monoclonal antibodies (MAbs) to neutrophil IgA Fc receptors. The MAbs will be used to study the biosynthesis of the receptor, characterize the binding site for IgA, and assess receptor internalization, degradation, or recycling. 2. Characterize the biological functions of neutrophil IgA Fc receptors activated by GM-CSF. Studies will be done to establish new models of IgA- mediated phagocytosis and ADCC in response to GM-CSF using micobial organisms and tumor cells. 3. Characterize the biochemical events in neutrophil IgA Fc receptor activation by GM-CSF. We will examine the role of protein synthesis, GTP binding proteins, changes in calcium fluxes, receptor phosphorylation, glycosylation, and receptor structure in response to GM-CSF. We will determine if IgA receptors are internalized and degraded, or recycled. 4. Clone the gene(s) encoding neutrophil IgA Fc receptors.