MONOCLONAL ANTIBODY ANALYSIS OF MACROPHAGE ACTIVATION

单核吞噬细胞系统的细胞与 具有多种免疫应答相关功能， 活动 其中包括参与主机防御， 肿瘤和感染性微生物，以及在阳性和 免疫反应的阴性对照。 的增强 在这些功能的发展中，巨噬细胞的活性是 调节，至少部分，由可溶性介质产生的过程中， 免疫反应的过程 一个因素表明， 有效的巨噬细胞活化能力是干扰素-γ; 然而，这一因素控制的机制 巨噬细胞功能仍有待阐明。 的目的 拟议的研究是为了了解分子 巨噬细胞活化的基础，通过免疫化学 分析与活化相关的细胞表面改变 巨噬细胞的数量 使用已建立的巨噬细胞 免疫线，异种单克隆抗体探针 将发展为细胞表面抗原， 用免疫干扰素治疗。 这些 然后将使用抗体对表面进行详细分析， 巨噬细胞中期的抗原表型 活化途径，并用于鉴定特异性抗原 其在杀肿瘤活性或抗原呈递中起作用 激活细胞的功能。 抗体也将被使用， 结合生物化学技术， 分子生物学功能相关基因产物 特征化 这样的抗体最终可以用于 巨噬细胞选择性操作的实用水平 在体内发挥作用。

The cells of the mononuclear phagocyte system are associated with a wide variety of immune response-related functions and activities. These include a participation in host defense against neoplasia and infectious organisms, and a role in the positive and negative control of immune responses. The potentiation of macrophage activity in the development of such functions is regulated, at least in part, by soluble mediators produced during the course of an immune response. One factor shown to have potent macrophage activating capability is interferon-gamma; however, the mechanisms by which this factor controls macrophage function remain to be elucidate. The objective of the proposed research is to gain an understanding of the molecular basis of macrophage activation, through the immunochemical analysis of cell surface alterations associated with the activation of macrophages by interferon. Using established macrophage cell lines for immunization, xenogeneic monoclonal antibody probes will be developed to cell surface antigens which are induced on macrphages by treatment with immune interferon. These antibodies will then be used in a detailed analysis of the surface antigen phenotype of macrophages at intermediate stages in the pathway of activation, and for identification of specific antigens which play a role in the tumoricidal activity or antigen-presenting cell function of activated cells. The antibodies will also be used, in combination with biochemical techniques, to detect and purify functionally relevant gene products for molecular characterization. Such antibodies ultimately may be useful on a practical level in the selective manipulation of macrophage function in vivo.