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Attempts to eliminate immunological Suppression associated with bacterial infections.

尝试消除与细菌感染相关的免疫抑制。

基本信息

批准号：
62570188
负责人：
DOHI Yoshitane
金额：
$ 1.54万
依托单位：
Osaka University Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570188/
关键词：
bacterial glycolipid 免疫抑制癩菌 Phenolic glycolipid-1

项目摘要

Various bacterial products have positive or negative effects on the immunological resistance of the host. Profound immunological suppression is observed in patients with lepromatous leprosy, in whose sera a unique glycolipid to Mycobacterium leprae, phenolic glycolipid (PGL-1), can be detected. We purified PGL-1 from the infected tissues of armadillos with Mycobacterium leprae, and ascertained the preparations by NMR. In vivo injection of the PGL-1 in a micell form into mice induced remarkable suppression in cell-mediated immunity: The inhibition of Con A-induced T cell proliferation and the inhibition of generation of allogenic killer T cells. Addition of the PGL-1 on the normal splenic cultures also resulted the suppression of Con A responses and generation of allogenic killer T cells. These suppression by PGL-1 were completely abrogated by the supplementaion with normal peritoneal macrophages, suggesting that the inhibition by PGL-1 was due to the injuries in macrophages.We also isolated a mycolic acid-containing glycolipid (GaGM) derived from Gordona aurantiaca, an acid-fast bacterium closely related with Mycobacterium. This glycolipid had simillar effects on the immunological responses in a micell form. However, liposomes containing GaGM enhanced generation of cytotoxic t cells, NK cells, and activity of antibody dependent cytotoxicity (ADCC). These results suggest that effects of gycolipids were affected by their forms for presentaion to the host.

各种细菌产物对宿主的免疫抵抗力有正面或负面的影响。麻风患者血清中可检测到一种针对麻风分枝杆菌的独特糖脂--酚性糖脂(PGL-1)。我们从麻风分枝杆菌感染的螳螂组织中提纯了PGL-1，并用核磁共振确证了所制备的制剂。体内注射胶束形式的PGL-1对小鼠的细胞免疫功能有明显的抑制作用：抑制ConA诱导的T细胞增殖和同种异体杀伤T细胞的生成。在正常脾细胞培养中加入PGL-1也能抑制ConA反应和同种异体杀伤T细胞的生成。用正常的巨噬细胞补充PGL-1可完全消除这种抑制作用，提示PGL-1的抑制作用是由于巨噬细胞的损伤所致。我们还从与分枝杆菌关系密切的抗酸细菌Gordona aurantiaca中分离到一种含有真菌酸的糖脂(GaGM)。这种糖脂以胶束形式对免疫反应有类似的影响。然而，含有GaGM的脂质体增加了细胞毒T细胞和NK细胞的产生，并增强了抗体依赖性细胞毒(ADCC)的活性。这些结果表明卵磷脂的作用受其呈现给寄主的形式的影响。