STUDY ON NEWLY IDENTIFIED MICROGLIAL CELL GROWTH FACTORS

我们对胸腺肌样细胞可能的生理作用很感兴趣，并成功克隆了这些细胞。在本研究中，我们发现肌样细胞产生各种细胞因子，如il -1 α， IL-6, IL-7，一种未表征的淋巴刺激因子和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100kDa因子。两种因子诱导的单核细胞系细胞在形态和表型上存在差异，也不同于M-CSF和GM-CSF诱导的单核细胞系细胞。计算机搜索分析表明，100kDa因子与biglycan的核心蛋白高度同源，而biglycan尚未被确定为生长因子。100kDa因子的生化和生物学特性表明，其生物活性存在于分子量为40kDa的核心蛋白分子上，提示糖胺聚糖和低聚糖链对单核细胞生长活性并不重要。另一方面，60-80 kDa因子似乎与真正的细胞因子没有同源性。我们已经成功地克隆了1kb的基因。我们目前正试图延长60-80 kDa基因克隆的序列，以产生重组因子。我们也对分析单核细胞系细胞产生异质性的机制感兴趣。我们相信这两个因子和其他细胞因子对单核细胞异质性的产生是重要的。提供异质单核细胞群，如小胶质细胞、库普弗细胞，可能是防御各种感染和肿瘤的重要事件。

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.