Bioprotection mechanisms by specific binding of globo-series glycosphingolipids to LPS receptors

分析了脂多糖诱导鞘糖脂的生物保护作用及其作用机制。特别地，通过分析LPS受体和Gb 4之间的结合特异性和相互作用，重点关注球状系列糖脂对LPS细胞毒性的抑制功能，来证明糖脂的新功能。观察到Gb 4与TLR-4/MD 2的特异性结合以及Gb 4对LPS信号的抑制。只有饱和脂肪酸形式的Gb 4与TLR-4/MD 2结合的事实以及免疫细胞化学和膜分子分级分离的结果表明，结合发生在脂筏中。注射LPS的小鼠给予Gb 4可使其从内毒素休克中恢复，提示Gb 4在临床领域的治疗应用的可能性。

Bioprotective functions and action mechanisms of glycosphingolipids induced by LPS were analyzed. In particular, demonstration of novel functions of glycolipids was aimed by analyzing binding specificity and interaction between LPS receptors and Gb4 with focus on the suppressive function of globo-series glycolipids to LPS cytotoxicity. Specific binding of Gb4 to TLR-4/MD2 and the suppression of LPS signals with Gb4 were observed. The fact that only Gb4 with saturated forms of fatty acids bound to TLR-4/MD2 as well as results of immunocytochemistry and of fractionation of membrane molecules suggested that the binding occurred in lipid rafts. Administration of Gb4 into LPS-injected mice could restore them from endotoxin shock, suggesting the possibility of therapeutic application of Gb4 in the clinical fields.