主体DNA酶通过中性粒细胞外陷防止血管封闭
Miguel Jiménez-Alcázar1, Chandini Rangaswamy1, Rachita Panda1
1Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Science (New York, N.Y.)
|December 2, 2017
概括
两个脱氧核糖酶 (DNases) 降解中性粒细胞外陷 (NETs),以防止血栓和器官损伤. 在严重的感染中,它们的缺失导致NET血栓形成,突出显示了对血管封闭的双重保护机制.
科学领域:
- 免疫学
- 血管生物学
- 生物化学
背景情况:
- 血小板和纤维素凝块是血液静止和血栓形成的主要机制.
- 中性粒细胞外细胞陷 (NETs),由中性粒细胞释放的DNA纤维组成,代表了血管封闭的非正规途径.
- 了解体内NETs的调节对于解决病理性血管事件至关重要.
研究的目的:
- 在体内识别控制中性粒细胞外陷 (NETs) 的宿主因素.
- 研究脱氧核糖酶 (DNases) 在NET降解和血管封闭中的作用.
- 研究严重感染中NET降解缺陷的临床相关性.
主要方法:
- 在无菌中性恋和败血症期间评估NET形成和降解的体内研究.
- 缺少DNase1和DNase1-like的小鼠的遗传分析
- 在严重细菌感染的患者样本中对NET降解的ex vivo评估.
主要成果:
- DNase1和DNase1-like3被确定为降解循环NET的关键酶.
- 缺少DNase1和DNase1-like3的小鼠表现出血管内NET形成,导致血管阻塞和器官损伤.
- 患有严重细菌感染的患者表现出体外NET降解功能受损,与血管内NET凝块形成相关.
结论:
- DNase1和DNase1-like 3通过清除NET从循环中提供必要的宿主防御.
- 这些DNase的双重缺乏导致了病理性NET驱动的血管封闭.
- DNase1和DNase1-like3的独立表达提供了对NET介导的血管损伤的冗余保护机制.
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