Chen D, Wu X Z, Wen Z Y
Department of Biophysics, Medical College of Peking University, Beijing, China.
Panminerva Med. 2008 Jun;50(2):177-83.
Sulfated polysaccharides, which frequently connect to core protein, are expressed not only on cell surface but also throughout the extracellular matrix. Besides providing structural integrity of cells, sulfated polysaccharides interact with a variety of sulfated polysaccharides-binding proteins, such as growth factors, cytokines, chemokines and proteases. Sulfated polysaccharides play two-edged roles, inhibitor and promoter, in immune response. Some sulfated polysaccharides act as the immunosuppressor by blocking inflammatory signal transduction induced by proinflammatory cytokines, suppressing the activation of complement and inhibiting the process that leukocytes adhere to and pass through endothelium. On the contrary, the interaction between immune cells and sulfated polysaccharides produced by bacteria, endothelial cells and immune cells initiate the occurrence of immune response. It promotes the processes of recognizing and arresting antigen, migrating transendothelium, moving into and out of immune organ and enhancing the proliferation of lymphocyte. The structure of sulfated polysaccharides, such as molecular weight and sulfated sites heterogeneity, especially the degree of disaccharide sulfation, position of the sulfate moiety and organization of sulfated domains, may play critical role in their controversial effects. As a consequence, the interaction between sulfated polysaccharides and sulfated polysaccharide-binding proteins may be changed by modifying the structure of sulfated polysaccharides chains. The administration of drug targeting sulfated polysaccharide-protein interaction may be useful in treating inflammatory related diseases.
硫酸化多糖通常与核心蛋白相连，不仅在细胞表面表达，还遍布细胞外基质。除了提供细胞的结构完整性外，硫酸化多糖还与多种硫酸化多糖结合蛋白相互作用，如生长因子、细胞因子、趋化因子和蛋白酶。硫酸化多糖在免疫反应中扮演着双刃剑的角色，既是抑制剂又是促进剂。一些硫酸化多糖通过阻断促炎细胞因子诱导的炎症信号转导、抑制补体激活以及抑制白细胞黏附并穿过内皮的过程来充当免疫抑制剂。相反，免疫细胞与细菌、内皮细胞和免疫细胞产生的硫酸化多糖之间的相互作用引发免疫反应的发生。它促进抗原识别与捕获、跨内皮迁移、进出免疫器官以及增强淋巴细胞增殖的过程。硫酸化多糖的结构，如分子量和硫酸化位点的异质性，尤其是二糖硫酸化程度、硫酸基团的位置和硫酸化结构域的组织，可能在其有争议的作用中起关键作用。因此，通过修饰硫酸化多糖链的结构可能会改变硫酸化多糖与硫酸化多糖结合蛋白之间的相互作用。针对硫酸化多糖 - 蛋白质相互作用给药可能有助于治疗炎症相关疾病。
