GLUCOCORTICOIDS, INTERFERON AND FC RECEPTORS

说明(摘自申请人的摘要)：糖皮质激素， 被广泛用于抑制免疫功能，是治疗的关键药物 自身免疫性疾病中出现免疫球蛋白Fc受体(Fc Gamma R) 发挥重要作用。然而，糖皮质激素的作用机制 ALTER FC GAMMA R功能仍不清楚。自从……的发展以来 区分三种主要Fc伽马的单抗(MAb) R型(Fc-Gamma 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协同作用，现在可以确定 调查过了。此外，cDNA和更多的mAb最近已经 开发了不仅区分主要的FC Gamma R类型，而且还 可能代表基因复制、交替加工的亚型 和异型差异。此外，利用这些单抗的方法 已经开发出允许测量数量和功能的 这些Fc伽马R类型和亚型中的大多数具有活动性。使用这个基地 关于试剂和方法，其中许多是由研究人员开发的，他建议 为阐明糖皮质激素、干扰素(干扰素-γ)、 并筛选出其他免疫细胞因子对各自表达和功能的影响 Fc Gamma R型和亚型。这些研究将包括定量流动 用流式细胞术检测单核细胞上表达的每个Fc-γR的数量， 巨噬细胞和中性粒细胞与糖皮质激素和/或 重组免疫细胞因子。将使用cdna探针来确定 激素对每个Fc-Gamma R特异的mRNA表达的影响。 功能分析将包括糖皮质激素对抗体依赖的影响 细胞毒性(ADCC)、吞噬、抗原处理和 通过每个FC Gamma R类型和子类型进行的演示。因为其他人 分子当然会影响吞噬细胞的功能，申请者将 两种干扰素-γ和糖皮质激素诱导的表面分子的特性 我们将使用新的单抗鉴定出的单核细胞。最后，为了 糖皮质激素调节作用的体外研究进展 Fc受体的表达和功能对体内髓系细胞激活的影响， 申请者将检查链球菌病患者的吞噬细胞。 咽炎。用它作为白细胞的天然活体模型系统 他会确定是否有类似的糖皮质激素 体内激活的吞噬细胞和细胞培养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 了解髓系细胞Fc之间相互关系的基础 伽玛受体与调节功能活动的激素影响 吞噬细胞。

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.