Induction of differentiation of human myelogenous leukemic cells and signal transduction

人粒细胞白血病细胞的诱导分化及信号转导

• 批准号: 04671369
• 负责人: TAKEDA Ken
• 金额: $ 1.41万
• 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: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671369/
• 关键词: myeloid leukemia; differentiation; TNF; TNF receptor; signal transduction; ADP-ribosylation; ML-1; macrophage; ヒト骨髄性白血病; レチノイン酸; GM-CSF; 顆粒球; 細胞死; ML-1細胞; マクロファージ; エンテロトキシン

Human myelogenous leukemic cells can be induced to differentiate into the monocyte/macrophage pathway by protein inducers called differentiation inducing factors. We have succeeded in purifing one of these factors from leukocyte conditioned medium and identified it as TNF.TNF interacts with target cells by binding to two receptors, 55 kDa and 75 kDa. We examined the functions of these two TNF receptors in induction of differentiation of ML-1 cells. Differentiation was monitored by assessing the appearance and accrual of various cellular markers that are usually associated with maturation of the monocytic elements. 1) The ratio of 55 kDa/75 kDa TNF receptors of ML-1 cells was 1/4.2) Bothe TNF receptors were involved in induction of differentiation of ML-1 cells. Stimulation of either receptor type alone could induce differentiation, but simultaneous stimulation of both receptors induced it more effectively.We also clarified that TNF synergistically induced differentiation of ML-1 cells in combination with certain bacterial toxins such as choleratoxin and enterotoxin. They acted via ADP-ribosylation of GTP-binding proteins that were coupled to certain effectors other than adenylate cyclase.

人类髓性白血病细胞可以通过称为分化诱导因子的蛋白质诱导剂诱导分化为单核/巨噬细胞途径。我们已经成功地从白细胞条件培养基中纯化出其中一个因子，并鉴定为TNF。TNF通过结合55 kDa和75 kDa两种受体与靶细胞相互作用。我们检测了这两种TNF受体在诱导ML-1细胞分化中的功能。通过评估通常与单核细胞成熟相关的各种细胞标记物的外观和累积来监测分化。1) ML-1细胞55 kDa/75 kDa TNF受体的比值为1/4.2)两种TNF受体均参与诱导ML-1细胞的分化。单独刺激任一受体均可诱导分化，但同时刺激两种受体诱导分化效果更好。我们还澄清了TNF与某些细菌毒素（如霍乱毒素和肠毒素）联合可协同诱导ML-1细胞分化。它们通过gtp结合蛋白的adp核糖基化起作用，这些蛋白与腺苷酸环化酶以外的某些效应物偶联。

项目成果

Takeda, K.and Iwamoto, S.: "TNF induces differentiation human myelogenous leukemic cells." Zouketsu Inshi. 3. 233-239 (1992)

Takeda, K. 和 Iwamoto, S.：“TNF 诱导人骨髓性白血病细胞分化。”

武田 健: "TNFとリンホトキシン" 現代医療. 26. 3903-3908 (1994)

Ken Takeda：“TNF 和淋巴毒素”现代医学 26. 3903-3908 (1994)。

武田 健: "癌に対する生体防御機構" 共和出版, 165(101-114) (1993)

Ken Takeda：“针对癌症的生物防御机制”协和出版社，165（101-114）（1993）

Takeda,K. et al: "Roles of two tumor necrosis factor receptors in induction of differentiation of ML-1 cells." Anticancer Res.13. 883-886 (1993)

武田，K.

武田,健: "サイトカインによる分化誘導療法" 医学のあゆみ. (in press). (1994)

Takeda, Ken：“使用细胞因子的分化诱导疗法”医学史（正在出版）。