Laboratory of Microbiology and Immunology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Int J Mol Sci. 2021 Sep 15;22(18):9961. doi: 10.3390/ijms22189961.
Asthma is an allergic disease that causes severe infiltration of leukocytes into the lungs. Leukocyte infiltration is mediated by the binding of sialyl Lewis X (sLe) glycans present on the leukocytes to E-and P-selectins present on the endothelial cells at the sites of inflammation. Here, we found that mouse eosinophils express sLe glycans, and their infiltration into the lungs and proliferation in the bone marrow were significantly suppressed by an anti-sLe monoclonal antibody (mAb) F2 in a murine model of ovalbumin-induced asthma. The percentage of eosinophils in the bronchoalveolar lavage fluid and bone marrow and serum IgE levels decreased significantly in the F2-administered mice. Levels of T helper type 2 (Th2) cytokines and chemokines, involved in IgE class switching and eosinophil proliferation and recruitment, were also decreased in the F2-administered mice. An ex vivo cell rolling assay revealed that sLe glycans mediate the rolling of mouse eosinophils on P-selectin-expressing cells. These results indicate that the mAb F2 exerts therapeutic effects in a murine model of allergen-induced asthma, suggesting that sLe carbohydrate antigen could serve as a novel therapeutic target for allergic asthma.
哮喘是一种过敏性疾病，可导致白细胞大量浸润肺部。白细胞浸润是由白细胞上的唾液酸化路易斯 X（sLe）聚糖与炎症部位内皮细胞上的 E 选择素和 P 选择素结合介导的。在这里，我们发现小鼠嗜酸性粒细胞表达 sLe 聚糖，并且在卵清蛋白诱导的哮喘小鼠模型中，抗 sLe 单克隆抗体（mAb）F2 显著抑制其向肺部浸润和在骨髓中的增殖。F2 给药小鼠的支气管肺泡灌洗液和骨髓中嗜酸性粒细胞的百分比以及血清 IgE 水平显著降低。参与 IgE 类别转换以及嗜酸性粒细胞增殖和募集的辅助性 T 细胞 2（Th2）细胞因子和趋化因子的水平也在 F2 给药小鼠中降低。体外细胞滚动实验表明，sLe 聚糖介导了小鼠嗜酸性粒细胞在表达 P 选择素的细胞上的滚动。这些结果表明，mAb F2 在变应原诱导的哮喘小鼠模型中发挥治疗作用，表明 sLe 碳水化合物抗原可作为治疗过敏性哮喘的新靶标。
