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STUDY ON NEWLY IDENTIFIED MICROGLIAL CELL GROWTH FACTORS

新发现的小胶质细胞生长因子的研究

基本信息

批准号：
06670681
负责人：
KIKUCHI Aiko
金额：
$ 1.41万
依托单位：
NATIONAL INSTITUTE OF NEUROSCIENCE,NCNP
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

We have been interested in possible physiological roles of thymic myoid cells and succeeded in cloning the cells. During the persent study, we have found that the myoid cells produce various cytokines, such asa IL-1alpha, IL-6, IL-7, an uncharacterized lymphostimulatory factor (s), and two novel monocytic cell growth factors ; the one is purified as a 60-80 kDa factor and the other one is a 100kDa factor. Monocytic lineage cells induced by the two factors were morphologically and phenotypically different from each other and also different from those induced by M-CSF and GM-CSF.Computor search analysis suggests that the 100kDa factor is highly homologous to the core protein of biglycan which has not been identified as a growth factor. Biochemical and biological characterization of the 100kDa factor indicate that the biological activity reside on core protein molecules with the molecular weight of 40kDa, suggesting that glycosaminoglycan and oligosaccharide chains are not important for monocyte growth activity. The 60-80 kDa factor, on the other hand, appeared not to have homology with the authentic cytokines. We have succeeded in cloning 1 kb of the gene. We are currently trying to extend the sequence of the 60-80 kDa gene clone to produce the recombinant factor. We are also interested in analyzing the mechanisms of generation of heterogeneity in monocytic lineage cells. We believe our two factors, together with other cytokines, are important for generation of heterogeneity in monocytic cells. To provide heterogenous monocytic cell populations, such as microglias, Kupffer cells, are probably significant events for defending self from various infections and neoplasms.

我们对胸腺肌样细胞可能的生理功能产生了兴趣，并成功地克隆了胸腺肌样细胞。在本研究中，我们发现肌样细胞产生多种细胞因子，阿萨IL-1 α，IL-6，IL-7，一种未知的淋巴细胞刺激因子，以及两种新的单核细胞生长因子，一种纯化为60-80 kDa因子，另一种纯化为100 kDa因子。两种因子诱导的单核细胞系细胞在形态和表型上均存在差异，与M-CSF和GM-CSF诱导的单核细胞系细胞也存在差异。计算机检索分析表明，100 kDa因子与双糖蛋白聚糖（biglycan）的核心蛋白高度同源，而双糖蛋白聚糖的核心蛋白尚未被鉴定为生长因子。100 kDa因子的生化和生物学特性表明，生物活性存在于分子量为40 kDa的核心蛋白分子上，表明糖胺聚糖和寡糖链对单核细胞生长活性并不重要。另一方面，60-80 kDa因子似乎与真实的细胞因子不具有同源性。我们已经成功地克隆了1 kb的基因。我们目前正试图延伸60-80 kDa基因克隆的序列以产生重组因子。我们也有兴趣在单核细胞系细胞的异质性产生的机制进行分析。我们相信，我们的两个因素，以及其他细胞因子，是重要的单核细胞异质性的产生。提供异质性单核细胞群，如小胶质细胞、枯否细胞，可能是防御各种感染和肿瘤的重要事件。