Immunosuppressive Siglec-E ligands on mouse aorta are up-regulated by LPS via NF-κB pathway
Immunosuppressive Siglec-E ligands on mouse aorta are up-regulated by LPS via NF-κB pathway
复制标题
LPS 通过 NF-kappa B 途径上调小鼠主动脉上的免疫抑制 Siglec-E 配体
DOI：
10.1016/j.biopha.2019.109760
复制
发表时间：
2020-02-01
影响因子：
7.5
通讯作者：
Jia, Yi
中科院分区：
文献类型：
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作者：
Liu, Hongmei;Zheng, Yu;Jia, Yi
Siglec-E是人Siglec-9的小鼠直系同源物，是一种免疫抑制细胞表面受体。Siglec-E和Siglec-9主要存在于嗜中性粒细胞、巨噬细胞和单核细胞上。当Siglec-E与其细胞外环境中的唾液酸聚糖配体结合时，它会阻止免疫细胞的炎症反应。本研究旨在探讨Siglec-E配体在E.方法：测定Siglec-E配体在小鼠主动脉上的分布、分子大小和糖蛋白种类，并鉴定其蛋白载体。在体内，在LPS处理后检测Siglec-E配体的表达，有或没有NF-κ B抑制剂施用。在体外，使用培养的原代小鼠主动脉内皮细胞（MAEC）来研究在有或没有NF-κ B抑制剂的情况下由LPS诱导的Siglec-E配体表达的变化。结果：Siglec-E配体是一种O-连接的唾液酸糖蛋白，分子量为70 ~ 300 kDa，广泛分布于小鼠主动脉和体外培养的MAECs上。在体内，Siglec-E配体的表达以NF-κ B信号通路依赖性方式响应于LPS处理而在小鼠腹膜中增加。在MAECs中，Siglec-E配体的表达也通过LPS经由NF-κ B信号传导途径增加。恶性脑肿瘤中的Siglec-E蛋白-1被鉴定为Siglec-E配体的多种蛋白载体之一，并且配体的聚糖参与LPS诱导的MAEC。值得注意的是，巨噬细胞与脂多糖处理的MAEC共孵育可诱导巨噬细胞凋亡并降低巨噬细胞吞噬作用，而阻断Siglec-E与Siglec-E配体的结合可完全逆转这一效应。结论：这些数据表明Siglec-E配体在响应脂多糖诱导的血管炎症时高度表达，并抑制巨噬细胞的免疫反应，这可能是一种干预血管炎症的治疗策略。
Aims: Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor. Both Siglec-E and Siglec-9 are primarily found on neutrophils, macrophages, and monocytes. When Siglec-E binds to sialoglycan ligands in its extracellular environment, it halts the immune cells' inflammatory responses. In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.Methods: The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified. In vivo, the expression of Siglec-E ligands was detected after LPS treatment, with or without NF-kappa B inhibitor administration. In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-kappa B inhibitors. MAECs induced by LPS were co-cultured with macrophages and the effect of increased expression of Siglec-E ligands analyzed.Results: Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70 - 300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro. In vivo, the expression of Siglec-E ligands was increased in mice aortas in response to LPS treatment in an NF-kappa B signaling pathway dependent manner. In MAECs, the expression of Siglec-E ligands was also increased by LPS via an NF-kappa B signaling pathway. Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS. Notably, co-incubation of macrophages with LPS-treated MAECs induced macrophage apoptosis and decreased macrophage phagocytosis, effects that were completely reversed by blocking Siglec-E binding to Siglec-E ligands.Conclusions: These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.