Inhibition of tumor metastasis and immunotherapy by a microbial polysaccharaide

微生物多糖抑制肿瘤转移及免疫治疗

• 批准号: 11650816
• 负责人: MIYAKE Katsuhide
• 金额: $ 2.18万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11650816/
• 关键词: Streptococcus agalactiae; Sialyllactosamine; Sialyl Lewis carbohydrate; L-selectin; MEL-14; セレクチン; 微生物多糖

Structure of type specific capsular polysaccharide from group B streptococci, Streptococcus agalactiae type Ia and Ib have branched sialyl lactosamines linked to a lactose polymer. This structure is very similar to those of sugar chains, which are expressed in mammalian cells. Sialyl Lewis carbohydrates and several gangliosides expressed in cancer and hematopoietic cells have the sialyl lactosamine structure. These mammalian sugar chains are known to play important roles in metastasis and activation of immune system. In this study, we investigated effects of the capsular polysaccharide from S.agalactiae on hematopoietic cells. These polysaccharides showed activation effect on T-cells. This effect was inhibited by addition of anti-capsular polysaccharide antisera. This fact indicated that the effects caused by the type specific polysaccharide was due to sugar chain, because this antisera recognizes only sugar chain. We next studied targets of the polysaccharides on T-cells. T-cells are known to express L-selectin which binds sialyl Lewis carbohydrates. By using anti-L-selectin antibody (NEL-14), we analyzed reaction of T-cells to the signals caused by MEL-14. MEL-14 did not show any stimulation of T-cells, but this antibody showed similar effects to capsular polysaccharides in the presence of other signals such as CD3 and CD28 stimulation. These facts suggested that the bacterial specific capsular polysaccharide may bind to L-selectin and other unknown receptors.

B组链球菌、Ia和Ib型无乳链球菌的类型特异性荚膜多糖的结构具有连接到乳糖聚合物的支链唾液酸乳糖胺。这种结构与哺乳动物细胞中表达的糖链非常相似。唾液酸路易斯碳水化合物和几种神经节苷脂在肿瘤和造血细胞中表达，具有唾液酸乳糖胺结构。这些哺乳动物糖链在免疫系统的转移和激活中发挥重要作用。在本研究中，我们研究了无乳链球菌被膜多糖对造血细胞的影响。这些多糖对T细胞具有激活作用。这种作用可被抗囊多糖抗血清所抑制。这一事实表明，类型特异性多糖的作用是由于糖链所致，因为这种抗血清只识别糖链。接下来，我们研究了多糖在T细胞上的靶点。已知T细胞表达L选择素，该选择素与唾液酸路易斯碳水化合物结合。用抗L-选择素抗体(NEL-14)分析T细胞对MEL-14信号的反应。MEL-14对T细胞无刺激作用，但该抗体在CD3、CD28刺激等其他信号存在下，表现出与囊膜多糖相似的作用。提示细菌特异性囊膜多糖可能与L-选择素等未知受体结合。