NOVEL MACROPHAGE DERIVED INTERFERON INDUCED CYTOKINES

该提案是一个项目的一部分，该项目的总体目标是确定 巨噬细胞产物对理解和 治疗癌症和其他临床疾病。差异化， 小鼠巨噬细胞样细胞cDNA文库的筛选 LINE已鉴定出11个增加的mRNA物种 暴露于伽马-干扰素后的丰度。这些基因中的两个 被命名为119/MIG和CRG-2的物种编码先前未描述的 一个新定义的小分泌蛋白家族的成员 包括血小板因子4，黑色素瘤生长刺激活性 (MGSA/GRO)和IL-8等。利用119/MIG cDNA探针构建一种新的 该家族的人类成员MIG-2已被发现。目的 本建议旨在研究119/MIG、CRG-2和MIG-2基因以及 蛋白质，以确定其生物活性。具体的 目的是：确定119/MIG和 CRG-2蛋白由核酸探针和抗体组成； 119/MIG和CRG-2蛋白的制备及纯化 119/MIG和CRG-2的结构和功能特性 使用纯化的蛋白质和抗体；完成 MIG-2基因和蛋白的初步鉴定及利用MIG-2 将鼠标工作扩展到人类系统。119/MIG、CRG-2和MIG-2是 巨噬细胞来源的、干扰素诱导的分泌细胞家族成员 其成员具有细胞生长调节活性的蛋白质和 免疫细胞被激活。这些关联使119/MIG、CRG-2和 感兴趣的MiG-2作为正常和肿瘤细胞的潜在调节因子 生长和免疫细胞激活，并作为影响的中介 干扰素，如激活巨噬细胞对肿瘤细胞的作用 细胞毒性。

This proposal is part of a project whose overall aim is to identify macrophage products of potential importance for understanding and treating cancer as well as other clinical disorders. Differential, screening of a cDNA library prepared from a mouse macrophage-like cell line has led to the identification of 11 mRNA species of increased abundance following exposure to gamma-interferon. Two of these mRNA species, designated 119/MIG and CRG-2 encode previously undescribed members of a newly-defined family of small secreted proteins that includes platelet factor 4, melanoma growth stimulatory activity (MGSA/gro) and IL-8 among others. Using the 119/MIG cDNA probe a new human member of the family, MIG-2, has been discovered. The purpose of this proposal is to study the 119/MIG, CRG-2 and MIG-2 genes and proteins in order to identify their biological activities. The specific aims are: to determine the tissues and cell types where the 119/MIG and CRG-2 proteins are made by using nucleic acid probes and antibodies; to prepare and purify the 119/MIG and CRG-2 proteins characterize the structure, and the functional properties of the 119/MIG and CRG-2 proteins using the purified proteins and antibodies; to complete the initial characterization of the MIG-2 gene and protein and use MIG-2 to extend the mouse work to human systems. 119/MIG, CRG-2 and MIG-2 are macrophage-derived, interferon-induced members of a family of secreted proteins whose members are active as regulators of cell growth and immune cell activation. These associations make 119/MIG, CRG-2, and MIG-2 of interest as potential regulators of normal and neoplastic cell growth and immune cell activation, and as mediators of the effects of the interferons, such as the activation of macrophages for tumor cell cytotoxicity.