中文摘要
Siglec-E主要表达在巨噬细胞和中性粒细胞上,经其糖蛋白配体激活后发挥显著的抗炎作用,但目前对该配体的研究很少。该糖蛋白配体的结构和功能具有组织特异性,申请人既往对呼吸道中该配体进行过深入研究。现通过预实验发现主动脉壁中有该糖蛋白配体的表达,且国际上尚未见任何报道。基于巨噬细胞和中性粒细胞在动脉粥样硬化形成过程中具有重要的作用,以及该配体对以上细胞炎症反应的调控作用,提示该配体可能参与主动脉局部免疫稳态的维持,并可能在动脉粥样硬化形成中具有作用。故本项目拟在阐明主动脉壁中Siglec-E糖蛋白配体表达基本特征的基础上,研究其生理学意义,并在模型动物上探索其在动脉粥样硬化发病过程中的作用。达到从糖生物学领域深入探讨主动脉局部炎症免疫稳态维持机制以及拓展理解炎症反应在动脉粥样硬化形成中作用机制的目的,并为将来进一步探寻通过抑制血管局部炎症反应进行动脉粥样硬化防治的新靶点提供理论和实验支持。
英文摘要
Siglecs are single-pass membrane proteins containing multiple extracellular immunoglobulin-like domains that mediate glycan binding and short cytoplasmic tails. Siglec-E is expressed on monocytes/macrophages and neutrophils, and negatively regulate the immune cells on which they are expressed. In the aorta, Siglec-E might be involved in the regulation of inflammation in diseases such as atherosclerosis. Atherosclerosis is now considered as an chronic inflammation disorder of the aorta, which involve activated monocytes/macrophages and neutrophils. During an ongoing immune response, the activated inflammatory cells come into contact with the appropriate siglec-E ligands on aorta, resulting in the inflammatory response subsiding. Knowing the molecular characteristics of human siglec ligands and control of their expression in human aorta during inflammation might provide additional insight into this pathway of immune system regulation in health and disease. In this study, we try to explore the molecular characteristics and the roles in modulation of local immune homeostasis of siglec-E ligand on aorta. Then we try to investigate the roles of siglec-E ligand in the formation of atherosclerosis.
