MONOCLONAL ANTIBODY ANALYSIS OF MACROPHAGE ACTIVATION

单核巨噬细胞系统的细胞是相关的 具有多种与免疫反应相关的功能和 活动。这些措施包括参与东道主防御 肿瘤和感染性生物体，以及在积极和 对免疫反应的消极控制。的强化作用 巨噬细胞的活性在这种功能的发展中是 至少部分地由过程中产生的可溶性介体调节 免疫反应的过程。有一个因素被证明具有 强大的巨噬细胞激活能力是干扰素-γ； 然而，这一因素控制的机制 巨噬细胞的功能仍有待阐明。该计划的目标是 建议的研究是为了了解分子 巨噬细胞激活的基础，通过免疫化学 与激活相关的细胞表面变化的分析 干扰素对巨噬细胞的影响。利用已建立的巨噬细胞 免疫品系，异种单抗探针 将发展成细胞表面抗原，这些抗原是在 用免疫干扰素治疗巨噬细胞。这些 然后将使用抗体对表面进行详细分析 慢性阻塞性肺疾病中期巨噬细胞的抗原表型 激活途径，并用于鉴定特定抗原 它们在杀瘤活性或抗原呈递中起作用 激活细胞的细胞功能。抗体也将被使用， 与生化技术相结合，检测和纯化 功能相关的分子基因产物 人物刻画。这种抗体最终可能对 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.