ホストDNAゼは,中性粒子の細胞外トラップによって血管閉塞を防ぐ
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
まとめ
2つのデオキシリボヌクレアース (DNases) は中性粒子の細胞外トラップ (NETs) を分解して,血栓や臓器損傷を防ぐ. 重度の感染症では,その欠乏がNETの凝固形成につながり,血管閉塞に対する二重の保護メカニズムを強調する.
科学分野:
- 免疫学
- 血管生物学
- 生物化学
背景:
- 血小板とフィブリン凝固は,血液静止と血栓形成の主なメカニズムです.
- 中性粒子が放出するDNA繊維で構成される中性粒子の細胞外トラップ (NET) は,血管閉塞の非正規の経路を表しています.
- NETsの調節を in vivoで理解することは,病理的血管事件に対処するために極めて重要です.
研究 の 目的:
- ニュートロフィルの細胞外トラップ (NETs) を in vivoで制御する宿主因子を特定する.
- NETの分解と血管閉塞におけるデオキシリボヌクレアース (DNases) の役割を調査する.
- 重度の感染症におけるNET分解の欠陥の臨床的関連性を調査する.
主な方法:
- 滅菌性中性愛症と血症におけるNETの形成と分解を評価するインビボ試験.
- DNase1とDNase1-likeが欠けているマウスの遺伝子解析
- 重度の細菌感染による患者サンプルにおけるNETの分解のex vivo評価.
主要な成果:
- DNase1とDNase1-like3は,循環中のNETを分解する重要な酵素として特定されました.
- DNase1とDNase1-like3の両方の欠乏したマウスは,血管内NET形成を示し,血管の阻害と臓器損傷を引き起こした.
- 重度の細菌感染症の患者は,静脈内静脈血栓形成と相関する,ex vivoでのNET分解の障害を示した.
結論:
- DNase1とDNase1-like3は,NETを循環から除去することで,重要な宿主防御を提供します.
- これらのDNaseの二重欠乏は,NETによる病理的血管閉塞を引き起こす.
- DNase1とDNase1-like3の独立した発現は,NET媒介による血管損傷に対する冗長的な保護メカニズムを提供します.
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