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

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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.