细胞内膜网膜蛋白72 调节整合蛋白Mac-1活动以影响中性粒细胞的招募
Yaofeng Li1, Xulin Xu1,2, Haoqing Jerry Wang3,4
1Department of Pharmacology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases (Y.L., X.X., L.L., L.W., C.F.), Huazhong University of Science and Technology, Wuhan, Hubei, China.
Arteriosclerosis, thrombosis, and vascular biology
|January 11, 2024
概括
细胞内膜网膜居住蛋白72 (ERp72) 通过催化二硫化物重新排列来调节中性粒细胞整合蛋白Mac-1的激活. 这一发现表明ERp72是中性粒细胞相关血管病变的潜在治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 在血管炎症期间,整合素对中性粒细胞的粘附和迁移至关重要.
- 醇交换机制调节整合素的功能.
- 醇异构酶ERp72在中性粒细胞的Mac-1调控中的作用尚不清楚.
研究的目的:
- 研究ERp72在调节中性粒细胞上Mac-1 (整体素αMβ2) 的功能中的作用.
- 阐明ERp72影响Mac-1活动的分子机制.
- 评估ERp72在中性粒细胞相关血管病变中的治疗潜力.
主要方法:
- 静脉内显微镜检测中性粒细胞在体内的行为.
- 流细胞计和静态粘附测试用于体外整合蛋白功能.
- 孔焦显微镜,共免疫沉和质谱法用于分析ERp72-Mac-1相互作用和二硫化物键.
- 生物膜力探测器测量Mac-1结合亲和力.
- 针对急性肺损伤的小鼠模型,以评估ERp72在体内发挥的作用.
主要成果:
- 缺乏ERp72的中性粒细胞显示Mac-1激活受损,导致粘附和爬行减少.
- 在中性粒细胞表面,ERp72直接与Mac-1相互作用,催化αM子单元中的二硫化键的减少.
- 再组合ERp72增强了Mac-1结合亲和力,并挽救了粘附缺陷.
- 在小鼠模型中,ERp72的删除改善了肺损伤和改善了生存率.
结论:
- 细胞外ERp72是通过二硫化物重组来调节Mac-1整合素活性的关键调节者.
- ERp72代表了治疗中性粒细胞相关血管病变的新型治疗标.
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