Antitumor activity of monocyte-macrophages and its potentiation in cancer patients

单核巨噬细胞的抗肿瘤活性及其在癌症患者中的增强作用

基本信息

批准号：
63570293
负责人：
SONE Saburo
金额：
$ 1.28万
依托单位：
Tokushima University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

The present studies were performed to elucidate the mechaniss by which human activated mosocyte-macrophages kill tumor cells. Membrane-associated interieukin 1alpha (IL-1alpha ) induced by synergistic actions of IFN-gamma and synthetic adjutant, was found to be a mediator of human monodyte-mediated tumor cell killing. Human alveolar macrophages and monocyte-derived macrophages had abilities to produce cell-associated IL-1alpa activity and tamior necrosis factor (TNF) more than blood sonocytes. We also found that human monocyte-mediated cytotoxicity against human selanona (A375) cells was mediated in part by a new tumor cytotoxic factor (KW, 30,000; PI 6), differing from IL-1 and TMF-alpha. Abilities of blood monocytes of lung cancer patients to express antitamor activity and to produce IL-1 were analyzed. The presence of lung cancer significantly increased the number of barvested blood monocytes. Spontaneous tumoricidel activity of these monocutes was slightly high as compared to those of healthy donors. Nevertheless, there was no difference in production of IL-1 between two groups. Blood monocutes of lung cancer patients were less cytotaxic than healthy donors subsequent to incubation with synthetic immunoadjuvant, but were as tomoricidal as those from healthy donors when activated with liposome-entrapped immunoadjuvant. Human II-2-activated killer cells were cytotoxic to alveolar macrophages and to macrophates matured by GM-CSF from blood sonocytes. These observations suggest that alveolar macrophages may play a critical role in situ regulation of pulmonary inflammatory and immune reactions through production of cell- associated IL-1alpha and INF.

进行了本研究，以阐明人类活化的摩洛西省巨噬细胞杀死肿瘤细胞的机械设备。被发现是由IFN-gamma和合成副官协同作用引起的膜相关的Interieukin 1alpha（IL-1Alpha），是人类单基介导的肿瘤细胞杀死的介体。人肺泡巨噬细胞和单核细胞衍生的巨噬细胞具有比血那核细胞产生与细胞相关的IL-1ALPA活性和毒性坏死因子（TNF）的能力。我们还发现，针对人类Selanona（A375）细胞的人单核细胞介导的细胞毒性部分是由新的肿瘤细胞毒性因子（KW，30,000; PI 6）介导的，与IL-1和TMF-Alpha不同。分析了肺癌患者的血液单核细胞表达抗抗药活性并产生IL-1的能力。肺癌的存在显着增加了肉眼血液单核细胞的数量。与健康捐助者相比，这些单局的自发性肿瘤活性略高。然而，两组之间的IL-1产生没有差异。肺癌患者的血单局部与合成免疫辅助孵育后的健康供体相比，健康供体的细胞to症较少，但是当用脂质体缠绕的免疫辅助剂激活时，与健康供体的供体类似于健康供体。人II-2激活的杀伤细胞是细胞毒性对肺泡巨噬细胞的细胞毒性，以及从血液声cs中从GM-CSF成熟的巨噬细胞。这些观察结果表明，肺泡巨噬细胞可能通过产生与细胞相关的IL-1Alpha和INF来对肺部炎症和免疫反应的原位调节起关键作用。