Analysis of immunosupprative meclauism of Lipocortiut in tuwcr-beurig hestsits expression and action in wan

脂皮质素在 wan 中 tuwcr-beurig hestsits 表达及作用的免疫抑制作用分析

• 批准号: 04807090
• 负责人: OHTANI Haruo
• 金额: $ 0.77万
• 依托单位: TOHOKU 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 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04807090/
• 关键词: Lipocortin-1; Immunosuppression; Cancer patient; サプレッサーマクロファージ

In this study, we have explored the expression of Lipocortin-1(LC1)in the human tissues and its role in self-defense mechanism against cancers. The results are as follows ; 1)By immunohistochemical study using operative specimens, LC1 was proved in the cytoplasma of the inflammatory cells(mainly Macrophages)in the matrix of the tumor. 2)By FACS analysis, the rate of both LeuM3 and LC1 positive cells in peripheral blood mononuclear cells(PBMC)derived from cancer patients and healthy volunteers were 20% and 5% respectively. 3) By Westem blot analysis, LC1 protein whose molecule was 35 or 37 KDa was detected in the malignant ascites of gastric carcinoma patients. 4)Various concentrations of recombinant mouse LC1(gamma-LC1)were added to the cultures of PBMC to evaluate the effects on mitogenic responses(Con A)in healthy donors. The mitogenic responses in the presense of LC1(0.2, 2.0, 20mug/ml)were severely lower(10%, 90%, 99%)as compared to those without LC1. Furthermore, the similar inhib … More itory effects on mitogenic responses were obtained when malignant ascites or culture supernatents of spleen cells from cancer patients were added to the cultures instead of LC1.5)These inhibitory effects on the mitogenic responses were reversed by the addition of anti-LC1 serum. 6)Mitogenic responses of PBMC in cancer patients showed a decrease of 30% over healthy donors. Preparation of PBMC from cancer patients using nylonwool column in order to remove adherent cells reversed the response to normal level.In cancer patients, LC1 is produced distinctly and it seemed to be concerned in immunosuppression in tomor-bearing hosts because of the peculiar suppressive activities of LC1 in mitogenic responses. It is also suggested that LC1 is expressed strongly in accordance with progress of tumor in tomor-bearing mice, therefore we are now trying to clarify the relationship between expression of LC1 and progress of tumors in cancer patients with an effort to detect LC1 protein quantatively in human serum. Less

本研究旨在探讨脂皮质素-1（Lipocortin-1，LC 1）在人体组织中的表达及其在机体抗肿瘤自我防御机制中的作用。结果如下：1）手术标本免疫组化染色证实LC 1位于肿瘤基质中炎性细胞（主要是巨噬细胞）的胞浆内。（2）流式细胞仪检测肿瘤患者和健康志愿者外周血单个核细胞（PBMC）中LeuM 3和LC 1的阳性细胞率分别为20%和5%。3)Westem blot检测胃癌患者腹水中LC 1蛋白，分子量为35和37 KDa。4)将不同浓度的重组小鼠LC 1（γ-LC 1）加入PBMC培养物中，以评价对健康供体促有丝分裂反应（Con A）的影响。LC 1（0.2、2.0、20 μ g/ml）作用下的促有丝分裂反应明显低于无LC 1作用的细胞（10%、90%、99%）。此外，类似的 ...更多信息 当向培养物中加入恶性腹水或来自癌症患者的脾细胞培养上清液而不是LC 1时，获得对促有丝分裂反应的暂时影响。5）这些对促有丝分裂反应的抑制作用被加入抗LC 1血清逆转。6)癌症患者PBMC的促有丝分裂反应比健康供体降低30%。用尼龙棉柱分离肿瘤患者PBMC，去除粘附细胞，可使PBMC的免疫反应恢复到正常水平，在肿瘤患者中，LC_1明显产生，由于LC_1对有丝分裂反应的特异性抑制作用，LC_1可能与肿瘤患者的免疫抑制有关。另外，在荷瘤小鼠中，LC 1的表达与肿瘤的进展密切相关，因此，我们现在试图通过检测人血清中LC 1的蛋白定量来阐明LC 1的表达与肿瘤患者肿瘤进展之间的关系。少

项目成果

小関廣明: "担癌生体における免疫抑制機構の解析" 第94回日本外科学会総会 1994.3.29〜3.31.

Hiroaki Koseki：“癌症携带体的免疫抑制机制分析”第94届日本外科学会年会1994.3.29-3.31。

小関廣明: "担癌生体における免疫抑制機構の解析" 日本外科学会誌発表予定.

Hiroaki Koseki：“癌症携带体的免疫抑制机制分析” 预定在日本外科学会杂志上发表。