Therapeutic trial of sialyl Lewis^x analogue on airway inflammation in asthma

在炎症部位，ICAM-1、VCAM-1、E-和P-选择素等黏附分子表达于内皮细胞表面，而Mac-1、VLA-4和sialyl Lewis^x表达于炎症细胞表面。这些分子相互作用，在细胞从血管到组织的运输中发挥着重要作用。在这一点上，唾液酸化Lewis^x类似物被认为是通过抑制选择素和唾液酸化Lewis^x之间的结合来抑制炎症反应。为了验证这一假设，我们评估了SLX类似物对实验性小鼠模型的病理变化的影响。致敏后，我们测定了经鼻给药后小鼠的反应，然后SLX类似物通过腹腔或鼻腔给药。与对照组相比，暴露于抗原的小鼠(阳性对照组)的支气管肺泡灌洗液中淋巴细胞比例增加。在接受唾液酸化路易斯^x治疗的小鼠中，它们显著低于阳性对照组。此外，根据以前的报道，唾液酸化Lewis^x组小鼠的组织学评分显著低于阳性对照组。免疫组织化学方法检测E-选择素和P-选择素在小鼠肺小动脉内皮细胞中的表达，提示E-选择素等选择素与唾液酸化Lewis^x之间的相互作用在小鼠肺内炎性细胞浸润中起重要作用，唾液酸化Lewis^x类似物可能是一种抑制肺炎症反应的治疗药物。

At the site of inflammation, adhesion molecules such as ICAM-1, VCAM-1, E- and P-selectins are expressed on the surface of endothelial cells, on the other hand, Mac-1, VLA-4 and sialyl Lewis^x are expressed on the surface of inflammatory cells. These molecules interact each other and play an important roles in traffic of cells from blood vessels to tissue. In this regard, sialyl Lewis^x analogue is hypothesized to suppress the inflammatory responses by inhibiting the binding between selectins and sialyl Lewis^x. To examine this hypothesis, we evaluated the effect of SLX analogue on pathological changes in the experimental mouse model.After sensitization, we determined the responses of mice with transnasally administered Micropolyspora faeni (Mf), then SLX analogue was delivered by intraperitoneally or administered transnasally. Mice exposed to antigen (positive control) showed the increases of the number of lymphocyte ratio in their bronchoalveolar lavage fluids to compare the controls. In mice treated with sialyl Lewis^x, they were significantly lower than those in positive control. In addition, histological scores of mice treated with sialyl Lewis^x, which were determined according to previous reports, were significantly lower than that of positive control. In addition, expression of E- and P- selectins in endothelial cells of pulmonary arterioles were evaluated with immunohistochemistry, These results suggested that the interaction between selectins, such as E-selectin, and sialyl Lewis^x play a critical role in inflammatory cell infiltration in the lung of mice, and sialyl Lewis^x analogue may be a possible therapeutic drug to suppress pulmonary inflammatory response.