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Bio-molecular Approaches to Mycobacterial

分枝杆菌的生物分子方法

基本信息

批准号：
03670209
负责人：
DOHI Yoshitane
金额：
$ 1.34万
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 (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

We isolated a mycolic acid-containing glycolipid, trehalose-2,3,6'-trimycolate ( TTM ) from an acid-fast bacterium, Gordona aurantiaca, and characterized its biological activity. Subcutaneous or intra-capsular (kidney) injection of the liposome-encapsulated preparation of TTM into mice generated similar histo-pathological changes at the injected sites as that at the infected foci of tubercle bacilli : Abscess formation with caesation necrosis, infiltration of macrophages and proliferation of fibroblasts around the abscess were observed in these lesions. Intravenous or intra-peritoneal injection of TTM-liposomes rendered peritoneal macrophages to be in an activated state. The activated macrophages lysed syngeneic tumor cells including mastocytoma, myeloma or lung cancer cells by cell-to-cell contact. In addition, they released inflammatory factors including hydrogen peroxide, interleukin-1 and tumor-necrosisfactor alpha, suggesting that the activated macrophages were playing a central role in caesation necrosis and/or abscess formation. Furthermore, this treatment was effective in vivo on tumor-bearing mice to prolong their survival times against intraperitoneal challenge of P815 mastocytoma cells or against metastatic Lewis' lung cancer cells in the lymph nodes.We also found that in the peritoneal exudate cells of the mice, which were injected intraperitoneally with TTM-liposomes, not only activated macrophages but also gamma-delta T lymphocytes were generated in a large number. Fluorescein-activated cell sorter analyses of the lymphocytes fraction of the peritoneal exudate cells revealed the gamma-delta T cells co-expressed alpha-beta antigen receptors on their surfaces. In addition, these T cells augmented the intra-cellular killing of salmonella in macrophages.

我们从抗酸细菌金雀花中分离出一种含有霉菌酸的糖脂——海藻糖-2,3,6′-三羧酸酯（TTM），并对其生物活性进行了表征。将脂质体包裹的TTM制剂皮下或囊内（肾）注射到小鼠体内，在注射部位产生的组织病理变化与结核杆菌感染灶相似：在这些病变中观察到脓肿形成并凝固坏死，巨噬细胞浸润和脓肿周围成纤维细胞增殖。静脉注射或腹膜内注射ttm脂质体使腹膜巨噬细胞处于激活状态。激活的巨噬细胞通过细胞间接触裂解同源肿瘤细胞，包括肥大细胞瘤、骨髓瘤或肺癌细胞。此外，它们还释放炎症因子，包括过氧化氢、白细胞介素-1和肿瘤坏死因子α，这表明活化的巨噬细胞在caesation necrosis和/或脓肿形成中起着核心作用。此外，该治疗在体内对荷瘤小鼠有效，可延长其抵抗P815肥大细胞瘤细胞腹腔内攻击或淋巴结转移性Lewis肺癌细胞的存活时间。我们还发现，在腹腔注射了ttm脂质体的小鼠腹膜渗出细胞中，不仅产生了大量活化的巨噬细胞，还产生了大量γ - δ T淋巴细胞。对腹膜渗出细胞淋巴细胞部分的荧光素激活细胞分选分析显示γ - δ T细胞在其表面共表达α - β抗原受体。此外，这些T细胞增强了巨噬细胞对沙门氏菌的细胞内杀伤。