GLUCOCORTICOIDS, INTERFERON AND FC RECEPTORS

糖皮质激素、干扰素和 FC 受体

• 批准号: 3231477
• 负责人: PAUL GUYRE
• 金额: $ 21.19万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3231477
• 关键词: Streptococcus; antibody receptor; antigen presentation; cell mediated cytotoxicity; cytokine; flow cytometry; glucocorticoids; hormone regulation /control mechanism; human subject; immunoglobulin G; interferons; leukocyte activation /transformation; macrophage; monocyte; nucleic acid probes; phagocytosis; pharyngitis; receptor expression; tissue /cell culture

DESCRIPTION (Adapted from applicant's abstract): Glucocorticoids, which are widely used to suppress immune function, are key agents for treatment of autoimmune disorders in which Fc receptors for IgG (Fc gamma R) appear to play a major role. However, the mechanisms by which glucocorticoids alter Fc gamma R functions remain unclear. Since the development of monoclonal antibodies (mAbs) that discriminate each of three major Fc gamma R types (Fc gamma RI, II and III), the specific effects of glucocorticoids, alone and in concert with immune cytokines, can now be definitively investigated. Moreover, cDNAs and additional mAbs have recently been developed that discriminate not only the major Fc gamma R types, but also subtypes that probably represent gene duplications, alternate processing and allotypic differences. Furthermore, approaches utilizing these mAbs have been developed that permit measurement of the number and functional activity of most of these Fc gamma R types and subtypes. Using this base of reagents and approaches, many developed by the investigator, he proposes to elucidate the effects of glucocorticoids, gamma interferon (IFN-gamma), and selected other immune cytokines on the expression and function of each Fc gamma R type and subtype. These studies will include quantitative flow cytometry to measure the number of each Fc gamma R expressed on monocytes, macrophages and PMN's that are cultured with glucocorticoids and/or recombinant immune cytokines. cDNA probes will be used to determine hormonal effects on expression of mRNA specific to each Fc gamma R. Functional assays will include glucocorticoid effects on antibody-dependent cellular cytotoxicity (ADCC), phagocytosis, and antigen processing and presentation mediated via each Fc gamma R type and subtype. Since other molecules certainly influence phagocyte functions, the applicant will characterize two IFN-gamma and glucocorticoid-inducible surface molecules of monocytes that we will have identified using new mAbs. Finally, to relate the in vitro findings on the role of glucocorticoids in regulation of Fc receptor expression and function to in vivo myeloid cell activation, the applicant would examine phagocytes from patients with streptococcal pharyngitis. Using this as a natural in vivo model system for leukocyte activation, he would determine whether there are similar glucocorticoid effects on phagocytes activated in vivo and those activated in cell culture by immune cytokines. The applicant states that these studies would provide a basis for understanding the interrelationships among myeloid cell Fc gamma R and the hormonal influences that regulate the functional activities of phagocytes.

描述（改编自申请人摘要）：糖皮质激素， 广泛用于抑制免疫功能，是治疗的关键药物， IgG的Fc受体（Fc γ R）出现的自身免疫性疾病 发挥重要作用。 然而，糖皮质激素 改变Fc γ R功能仍不清楚。 发展至今 区分三种主要Fc γ R型（Fc γ RI、II和III），糖皮质激素的特异性作用， 单独和与免疫细胞因子一起，现在可以明确地 研究了 此外，cDNA和额外的mAb最近已经被用于治疗癌症。 开发了不仅区分主要Fc γ R类型， 可能代表基因复制的亚型，交替处理 和同种异型差异。 此外，利用这些mAb的方法 已经开发了允许测量的数量和功能 这些Fc γ R类型和亚型中的大多数的活性。 利用这个基地 他提出，许多试剂和方法是由研究人员开发的， 为了阐明糖皮质激素、γ干扰素（IFN-γ）的作用， 并选择其他免疫细胞因子对每种细胞因子的表达和功能进行研究。 Fc γ R类型和亚型。 这些研究将包括定量流动 流式细胞术以测量单核细胞上表达的每种Fc γ R的数量， 巨噬细胞和PMN与糖皮质激素和/或 重组免疫细胞因子。 cDNA探针将用于确定 激素对每种Fc γ R特异性mRNA表达的影响。 功能测定将包括糖皮质激素对抗体依赖性 细胞毒性（ADCC）、吞噬作用和抗原加工， 通过每种Fc γ R类型和亚型介导的呈递。 因为其他 分子肯定会影响吞噬细胞的功能，申请人将 表征两种IFN-γ和糖皮质激素诱导的表面分子 我们将用新的单克隆抗体鉴定单核细胞。 最后为 将糖皮质激素在调节中的作用的体外发现与 Fc受体表达和功能对体内髓样细胞活化的影响， 申请人将检查链球菌患者的吞噬细胞 咽炎。 使用此作为白细胞的天然体内模型系统 激活，他会确定是否有类似的糖皮质激素 对体内激活的吞噬细胞和细胞培养物中激活的吞噬细胞的影响 通过免疫细胞因子。 申请人表示，这些研究将提供 理解髓样细胞Fc之间相互关系的基础 γ R和调节功能活动的激素影响 吞噬细胞