CD177在ANCA相关小血管炎发病机制中的作用

项目名称： CD177在ANCA相关小血管炎发病机制中的作用

项目编号： No.81501392

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 胡楠

作者单位： 北京大学

项目金额： 18万元

中文摘要： ANCA相关小血管炎的发病机制尚不明确。目前认为ANCA自身抗原在炎症状态下表达于中性粒细胞膜表面，被ANCA识别并引起中性粒细胞呼吸爆发，导致临近血管内皮损伤，组织病理表现为坏死性血管炎。活性氧自由基的非特异性损伤局限于中-小血管，提示中性粒细胞粘附、游出血管内皮的过程是发病的重要阶段。蛋白酶3（Proteinase 3, PR3）是ANCA自身抗原，以CD177为受体表达于中性粒细胞膜表面。CD177属糖蛋白（PECAM1配体），具有粘附分子功能。我们的前期工作证实CD177在AAV患者中表达增加。根据CD177与PECAM1的配体关系，我们推测1）CD177+中性粒细胞在炎症发生时，粘附、游出血管内皮更迅速；2）在中性粒细胞游出过程中，CD177与PECAM-1的结合，导致其配体PR3的释放，并在ANCA作用下，加重内皮细胞损伤。

中文关键词： 自身免疫性；呼吸爆发；血管炎；中性粒细胞；CD177

英文摘要： The pathogenesis of ANCA-associated systemic vasculitis (AAV) has not been fully demonstrated. It has been descripted that ANCA antigens are brought to the neutrophil surface after priming by inflammatory cytokines, which are recognized by ANCA. Then, the oxidative spices are released, which directly damage the vessel wall immediately adjacent. The pathological feature of AAV is necrosis of endothelial cells of small-to-medium sized vessels where adhesion and transmigration may take place, highlighting the importance of these processes in disease development. Proteinase 3, one of the ANCA antigens, is presented on the cell surface by CD177, which is a glycoprotein. CD177 may interact with PECAM1 on endothelial cells and play a role as an adhesion molecule. Based on recent findings on this subject, we hypothesize that 1) neutrophils expressing CD177 are more efficient in adhesion and transmigration; 2) PR3 are released during CD177-PECAM1 interaction, and may cause extra damage to the vessel wall when ANCA in presence.

英文关键词： autoimmunity;respiratory burst;vasculitis;neutrophil;CD177