Application of sialyl-Lewis X conjugated liposome to the murine experimental autoimmune uveoretinitis

（目的）本研究旨在探讨Sialyl-Lewis X偶联脂质体（SLX（+）脂质体）在小鼠实验性自身免疫性葡萄膜视网膜炎（EAU）中的分子功能，并探讨其是否可能成为以e -选择素为分子靶点的活性靶向给药系统（ATDDS）。（方法）对脂质体进行器官分布分析。（表1）给EAU小鼠注射异硫氰酸荧光素（FITC）标记的SLX（+）脂质体，观察到FITC荧光在脉络膜和视网膜上的积累。以正常小鼠为对照。使用不结合SLX的脂质体（SLX（-）脂质体）进行了相同的实验。（表2）对EAU小鼠眼内e -选择素进行免疫染色。我们检查了它是否与FITC标记的SLX（+）脂质体的积累部分相同。（表3）EAU小鼠经抗e -选择素中和抗体后，注射FITC标记的SLX（+）脂质体。观察到SLX（+）脂质体对e -选择素的结合抑制作用。（结果）仅在给EAU小鼠注射SLX（+）脂质体时，才观察到FITC的积累。FITC的积累与E-selectin的表达一致。e -选择素中和抗体抑制了SLX（+）脂质体与e -选择素的结合。（讨论）SLX是白细胞表面的一种低聚糖，已知与血管内皮细胞上的e -选择素结合。我们的研究结果表明，SLX（+）脂质体在炎症部位的作用与白细胞相似。这种靶向e -选择素的SLX偶联脂质体可能具有ATDDS的作用。

(Purpose)The purposes of this study are to investigate the molecular function of Sialyl-Lewis X conjugated liposome (SLX (+) liposome) in murine experimental autoimmune uveoretinitis (EAU) and to examine whether it may become the active targeting drug delivery system (ATDDS) aiming at E-selectin as a molecule the target.(Methods)For organ distribution analysis of liposome, three experiments were performed. (Exp.1) Fluorescein isothiocyanate (FITC) labeled SLX (+) liposome was administered to EAU mice and accumulation of FITC fluorescence to the choroid and retina was observed. Normal mice were used as controls. Same experiments using the liposome which does not conjugate SLX (SLX (-) liposome) were performed. (Exp.2) Immunostaining of E-selectin in the eye of EAU mice were performed. We examined whether it would be the same as the accumulation part of the FITC labeled SLX (+) liposome. (Exp.3) After administration of anti E-selectin neutralization antibody to EAU mice, FITC labeled SLX (+) liposome was injected to EAU mice. Binding inhibition of SLX (+) liposome to E-selectin was observed.(Results)Accumulation of FITC was observed only when EAU mice were administered with SLX (+) liposome. Accumulation of FITC was in agreement with E-selectin expression. Binding of SLX (+) liposome to E-selectin was inhibited by neutralization antibody to E-selectin.(Discussion)SLX, an oligosaccharide on the surface of a leukocyte, is known to combine with E-selectin on the vascular endothelial cells. Our results suggest that SLX (+) liposome operates similarly to leukocytes at the site of inflammation. This SLX conjugated liposome that targets at E-selectin might serve as ATDDS.