Inhibition of tumor metastasis and immunotherapy by a microbial polysaccharaide

来自B组链球菌、Ia型和Ib型无乳链球菌的类型特异性荚膜多糖的结构具有与乳糖聚合物连接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。唾液酸刘易斯碳水化合物和几种在癌症和造血细胞中表达的神经节苷脂具有唾液酸乳糖胺结构。已知这些哺乳动物糖链在转移和免疫系统激活中起重要作用。本研究探讨了无乳链球菌荚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。这种作用被抑制的抗荚膜多糖抗血清。这一事实表明，型特异性多糖引起的影响是由于糖链，因为这种抗血清只识别糖链。我们接下来研究了多糖在T细胞上的靶点。已知T细胞表达结合唾液酸刘易斯碳水化合物的L-选择素。通过使用抗L-选择素抗体（NEL-14），我们分析了T细胞对MEL-14引起的信号的反应。MEL-14没有显示出对T细胞的任何刺激，但是该抗体在其他信号如CD 3和CD 28刺激的存在下显示出与荚膜多糖相似的作用。这些事实表明，细菌特异性荚膜多糖可能与L-选择素和其他未知受体结合。

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.