Author/Authors :
Yamamoto، نويسنده , , Yoshiteru and Sahara، نويسنده , , Hiroeki and Takenouchi، نويسنده , , Mika and Matsumoto، نويسنده , , Yoshitaka and Imai، نويسنده , , Akihito and Fujita، نويسنده , , Tatsuya and Tamura، نويسنده , , Yasuaki and Takahashi، نويسنده , , Nobuaki and Gasa، نويسنده , , Shinsei and Matsumoto، نويسنده , , Kenjiro and Ohta، نويسنده , , Keisuke and Sugawara، نويسنده , , Fumio and Sakaguchi، نويسنده , , Kengo and Jimbow، نويسنده , , Kowichi and Sato، نويسنده , , Noriyuki، نويسنده ,
Abstract :
We previously reported that synthetic sulfo-glycolipid, 3-O-(6-deoxy-6-sulfono-β-d-glucopyranosyl)-1,2-di-O-acylglycerol (β-SQDG(18:0)) which was deduced from sulfonoquinovosyl-diacylglycerols of sea urchin possessed immunosuppressive effects, such as human mixed lymphocyte reaction (MLR) and skin allograft in rat, and that these effects were caused by contact inhibition between T-cells and antigen presenting cells (APCs). Here, we investigated the mechanism of these immunosuppressive effects on human MLR by β-SQAG9 which had been newly synthesized from β-SQDG(18:0) to improve structural stability in water solution. CD62L+ T-cells in peripheral blood predominantly respond to APCs, and β-SQAG9 inhibited the response of CD62L+ T-cell subset in human allogeneic MLR. Surprisingly, it was demonstrated that β-SQAG9 bound to L- and P-selectin (CD62L and P) molecule in vitro. Meanwhile, β-SQAG9 efficiently formed liposome structure and bound to L-selectin on the cell surface of CD62L+ T-cell subset but might not be incorporated into the cells. Because the immunosuppressive effects of β-SQAG9 disappeared when β-SQAG9 liposome was changed to soluble form by detergent, the liposome structure of β-SQAG9 was presumed to be essential for these effects. These findings suggested β-SQAG9 to be a novel drug with a unique immunosuppressive action.
Keywords :
MLR , Sulfoglycolipid , Immunosuppresive drug , L-selectin , CD62L+ T-lymphocyte