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Studies on differentiation inducing factors for human myelogenous leukemic cells and enhancement of their activity.

人粒细胞白血病细胞分化诱导因子及其活性增强的研究。

基本信息

批准号：
61571067
负责人：
TAKEDA Ken
金额：
$ 1.28万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

Human myelogenous leukemic cells can be induced to differentiate into the monocyte/macrophage pathway by various chemicals and protein inducers called differentiation inducing factors(DIF). However, human DIF has not yet been well characterized. We have tried to purified DIFs from eadia conditioned by PHA-stimulated lymphocytes and fibroblasts in this project.We have succeeded to purify a DIF homogeneity from lymphocyte conditioned medium. The purified DIF has a relative molecular mass of approximately 17,000, with an NH_2-terminal sequence the same as that of human tumor necrosis factor(TNF). We have also succeeded to purigy a fibroblast-derived differentiation inducing factor(F-DIF) from medium conditioned by a human fibroblast cell line(WI-26VA4). The purified DIF had a molecular weight of about 27,000 determined by SDS-PAGE, with an HN_2-terminal sequence the same as that of human interleukin-6(IL-6) except for the absence of the N-terminal proline. F-DIF synergistically induced differentiation of human myelogenous leukemic cell lines when combined with TNF.F-DIF synergistically enhanced the differentiation of human myelogenous leukemic cell lines when combined with TNF. TNF and IL-6 synergistically enhanced the differentiation in combination with other biological response modifiers such as prostaglendin E_2, retinoic acid, vitamid D_3, interferon- , etc.The results presented in this project point to another new biological effects of TNF and IL-6. This could be one of the regulatory signals that control cellular reactions during infection. Combination use of cytokines and BRM may play in effecting terminal differentiation of the clinical leukemias.

人骨髓性白血病细胞可以被称为分化诱导因子（DIF）的各种化学物质和蛋白质诱导剂诱导分化为单核细胞/巨噬细胞途径。然而，人类DIF尚未得到很好的表征。本课题尝试从PHA刺激的淋巴细胞和成纤维细胞条件培养液中纯化DIF，并成功地从淋巴细胞条件培养液中纯化出DIF。纯化的DIF相对分子质量约为17，000，其NH_2端序列与人肿瘤坏死因子（TNF）相同。我们还成功地从人成纤维细胞系（WI-26 VA 4）的条件培养基中纯化了成纤维细胞衍生的分化诱导因子（F-DIF）。经SDS-PAGE测定，纯化的DIF分子量约为27，000，其HN_2端序列与人白细胞介素-6（IL-6）的序列相同，只是N端缺少脯氨酸。当与TNF组合时，F-DIF协同诱导人髓性白血病细胞系的分化。当与TNF组合时，F-DIF协同增强人髓性白血病细胞系的分化。TNF和IL-6与其它生物反应调节剂如E_2、维甲酸、维生素D_3、干扰素等协同促进分化，提示TNF和IL-6的另一种新的生物学效应。这可能是感染期间控制细胞反应的调节信号之一。细胞因子与BRM联合应用可能对临床白血病的终末分化起作用。