Activation and regulation of macrophages by Cryo-destructed tumor cells

冷冻破坏肿瘤细胞对巨噬细胞的激活和调节

• 批准号: 04454499
• 负责人: SAKUDA Masayoshi
• 金额: $ 3.26万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454499/
• 关键词: Cryosurgery; Macrophage; Immunological regulation; Interferon; Tumor immunity; 細胞性免疫; サイトカイン

We investigate the immunological responses, especially about macrophages elicited by cryo-destructed Meth A(Cryo-MA) or Mitomycin C-treated Meth A(MMC-MA) as a model experiment of cryosurgery against malignant tumor.Spleen cells of Cryo-MA inoculated mice showed antitumor activity in Winn assay, but higher activity was observed in MMC-MA inoculated mice. The effecter cells induced by Cryo-MA were macrophages and natural killer(NK) cells, although MMC-MA increased the activity of macrophases and cytotoxic T lymphocytes (CTL). The appearance of macrophages' cytostatic activity was delayd in Cryo-MA arm compared with MMC-MA arm.Macrophages of Cryo-MA arm enhanced the producing activity of interleukin-1, alpha-interferon(IFN) and prostaglandin E2. Macrophages of MMC-MA arm enhanced the production of TNF and increased Ia antigen positive ratio. These findings suggest that macrophages of both groups are activated different immunological mechanisms. It was found that Cryo-MA playd a role as an alpha-interferon inducer, and the macrophages stimulated with Cryo-MA produced alpha-IFN in vitro. Intraperitoneal administration of the anti-alpha-IFN antibody carried down-regulation of macrophage cytostatic and NK activity of Cryo-MA inoculated mice, whereas MMC-MA mice were not. CTL activity enhanced some extent by administration of anti-alpha-IFN antibody. These facts suggest that the alpha-IFN have two ways of immunological regulation, the first one is the activation of cytostatic activity of macrophage and NK activity, and the other is down-regulation of CTL activity by suppression of Ia antigen expression of macrophages.

本文以冷冻灭活甲氨蝶呤（Meth A，Cryo-MA）和丝裂霉素（MMC）处理的甲氨蝶呤（Meth A，MMC）作为冷冻治疗恶性肿瘤的模型，研究了Cryo-MA和MMC处理的甲氨蝶呤（Meth A，MMC）诱导的小鼠脾细胞免疫反应，发现Cryo-MA处理的小鼠脾细胞在Winn法中显示出抗肿瘤活性，而MMC处理的小鼠脾细胞的抗肿瘤活性高于Cryo-MA。Cryo-MA诱导的效应细胞是巨噬细胞和自然杀伤（NK）细胞，但MMC-MA可增加巨噬细胞和细胞毒性T淋巴细胞（CTL）的活性。与MMC-MA组相比，Cryo-MA组巨噬细胞抑制活性的出现延迟，Cryo-MA组巨噬细胞产生白细胞介素-1（IL-1）、α-干扰素（IFN）和前列腺素E_2（PGE_2）的活性增强。MMC-MA组巨噬细胞可促进TNF的产生，提高Ia抗原阳性率。这些结果表明，两组的巨噬细胞激活不同的免疫机制。结果表明，Cryo-MA具有α-干扰素诱导剂的作用，经Cryo-MA刺激的巨噬细胞在体外产生α-干扰素。腹腔注射抗α-IFN抗体可下调Cryo-MA接种小鼠的巨噬细胞抑制活性和NK活性，而MMC-MA小鼠则无此作用。抗α-IFN抗体可使CTL活性有一定程度的增强。提示α-IFN有两种免疫调节途径，一种是激活巨噬细胞的细胞抑制活性和NK活性，另一种是通过抑制巨噬细胞Ia抗原表达下调CTL活性。

项目成果

Tetsuo Ohnishi: "Intracerebroventricular treatment of mice with pertussis toxin induces hyperalgesia and enhances ^3H-nitrendipine binding to synaptic membranes:similarity with morphine tolerance." Naunyn-Schmiedeberg's Arch Pharmacol. 341. 123-127 (1990)

Tetsuo Ohnishi：“用百日咳毒素对小鼠进行侧脑室内治疗可诱导痛觉过敏并增强 ^3H-尼群地平与突触膜的结合：与吗啡耐受性相似。”

作田 正義: "口腔外科学(分担執筆・編集代表 宮崎 正)" 738 (1988)

作田正义：《口腔外科（撰稿人/主编：宫崎正）》738 (1988)

Souichi Iwai: "Changes in Hox1.6,c-jun,and Oct-3 gene expressions are associated with teratocarcinoma F9 cell differentiation in three different ways of induction" Exp.Cell Res.205. 39-43 (1993)

Souichi Iwai：“Hox1.6、c-jun 和 Oct-3 基因表达的变化与畸胎瘤 F9 细胞以三种不同诱导方式分化相关”Exp.Cell Res.205。

作田 正義: "下顎悪性腫瘍の病態とその処置法" 日本口腔外科学会雑誌. 35. 1705-1709 (1989)

Masayoshi Sakuta：“下颌恶性肿瘤的病理学及其治疗方法”日本口腔颌面外科学会杂志35。1705-1709（1989）。

中澤光博: "下顎歯肉扁平上皮癌の顎骨吸収様式と予後との関連性" 日本口腔科学会雑誌. 40. 589-599 (1991)

Mitsuhiro Nakazawa：“下颌牙龈鳞状细胞癌颌骨吸收模式与预后的关系”日本口腔医学会杂志 40. 589-599 (1991)。