MEMBRANE-FORM TUMOR NECROSIS FACTOR : ANALYSIS AND CLINICAL APPLECATION OF ACTIVATED ALVEOLAR MACROPHAGES

膜型肿瘤坏死因子:活化肺泡巨噬细胞的分析及临床应用

• 批准号: 03670323
• 负责人: SONE Saburo
• 金额: $ 1.34万
• 依托单位: UNIVERSITY OF TOKUSHIMA, SCHOOL OF MAEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670323/
• 关键词: membrane TNF-alpha, alveolar macrophages, cytotoxicity, lung cancer; 肺胞マクロファージ; 細胞障害; 肺癌; サイトカイン; 膜型腫瘍壊死因子; マクロファージ; TNF; インターロイキン-4; 活性酸素; マクロファ-ジ; 抗腫瘍活性; 腫瘍壊死因子; インタ-ロイキン・4

The expressions of a membrane form TNF (m-TNF) by human alveolar macrophages (AM) and autologous blood monocytes from healthy donors were examined. Upon lipopolysaccharide (LPS) stimulation, AM produced 26-kDa TNF-alpha on thier cell surface. We designed a bioassay for measuring m-TNF in which macrophages were fixed with paraformaldehyde after stimulation for 18hr, then m-TNF activity was assessed as cytotoxicity of fixed macrophages on L929 cells. on LPS istmulation, AM produced significant amounts of m-TNF earlier than TNF-alpha secretion. Interleukin-4 suppressed both m-TNF producition and TNF-alpha secretion. Although blood monocytes produced small amounts of m-TNF, monocyte-derived macrophages showed enhanced m-TNF after cultivation with GM-CSF for 10 days. as a biological activity, m-TNF on activated monocytes significantly augmented interleukin-6 production by a lung cancer cell line, RERF-LC-OK cells. These findings suggest that m-TNF may play important roles in exhibition of amcrophage functions in situ.

检查了人肺泡巨噬细胞 (AM) 和来自健康供体的自体血单核细胞的膜形式 TNF (m-TNF) 的表达。在脂多糖 (LPS) 刺激下，AM 在细胞表面产生 26-kDa TNF-α。我们设计了一种测量 m-TNF 的生物测定法，其中巨噬细胞在刺激 18 小时后用多聚甲醛固定，然后将 m-TNF 活性评估为固定巨噬细胞对 L929 细胞的细胞毒性。在 LPS 刺激下，AM 比 TNF-α 分泌更早产生大量 m-TNF。 Interleukin-4 抑制 m-TNF 的产生和 TNF-α 的分泌。虽然血液单核细胞产生少量的 m-TNF，但单核细胞来源的巨噬细胞在用 GM-CSF 培养 10 天后显示出增强的 m-TNF。作为一种生物活性，活化的单核细胞上的 m-TNF 显着增强了肺癌细胞系 RERF-LC-OK 细胞的白细胞介素 6 的产生。这些发现表明 m-TNF 可能在原位巨噬细胞功能的发挥中发挥重要作用。

项目成果

Yasuhiko Nishioka: "Downーregulation by Interleukin 4 of activation of human alveolar macrophages to the tumoricidal state." Cancer Research. 51. 5526-5531 (1991)

Yasuhiko Nishioka：“白细胞介素 4 下调人类肺泡巨噬细胞的杀肿瘤状态。” 51. 5526-5531 (1991)。

仁井 昌彦: "ヒト肺胞マクロファージのモノカイン産生動態とIL・4によるその調節作用" Biotherapy. 5. 441-445 (1991)

Masahiko Nii：“人肺泡巨噬细胞中单核因子产生的动力学及其通过 IL-4 的调节作用”生物疗法 5. 441-445 (1991)。

Geetha Bhaskaran: "Differential effects of interleukin‐4 on superoxide anion production by humen alveolar macrophages stimulated with lipopolysaccharide and interferon‐γ" Journal of Leukocyte Biology. 52. 218-223 (1992)

Geetha Bhaskaran：“白细胞介素 4 对脂多糖和干扰素 γ 刺激的人肺泡巨噬细胞产生超氧阴离子的不同影响”白细胞生物学杂志 52. 218-223 (1992)。

Akihiko Nii: "Induetion of a 26-KDa membrane‐form tumor necrosis factor(TNF)-α in human alveolar macrophages" Journal of Leukocyte Biology. 53. (1993)

Akihiko Nii：“人肺泡巨噬细胞中 26-KDa 膜型肿瘤坏死因子 (TNF)-α 的诱导”，白细胞生物学杂志 53。(1993)