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首页> 外文期刊>Nature >Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death
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Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death

机译：外蛋白组蛋白H4通过诱导裂解细胞死亡来协调慢性炎症

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摘要

The perpetuation of inflammation is an important pathophysiological contributor to the global medical burden. Chronic inflammation is promoted by non-programmed cell death(1,)(2); however, how inflammation is instigated, its cellular and molecular mediators, and its therapeutic value are poorly defined. Here we use mouse models of atherosclerosis-a major underlying cause of mortality worldwide-to demonstrate that extracellular histone H4-mediated membrane lysis of smooth muscle cells (SMCs) triggers arterial tissue damage and inflammation. We show that activated lesional SMCs attract neutrophils, triggering the ejection of neutrophil extracellular traps that contain nuclear proteins. Among them, histone H4 binds to and lyses SMCs, leading to the destabilization of plaques; conversely, the neutralization of histone H4 prevents cell death of SMCs and stabilizes atherosclerotic lesions. Our data identify a form of cell death found at the core of chronic vascular disease that is instigated by leukocytes and can be targeted therapeutically.
机译：炎症的永久性是全球医疗负担的重要病理学贡献者。通过非编程的细胞死亡（1，）（2）促进慢性炎症;然而，如何煽动炎症，其细胞和分子介质，其治疗价值不足。在这里，我们使用动脉粥样硬化的小鼠模型 - 全世界死亡率的主要潜在原因 - 以证明细胞外组蛋白H4介导的平滑肌细胞（SMC）触发动脉组织损伤和炎症。我们表明激活的损伤SMC吸引中性粒细胞，触发含有核蛋白的中性粒细胞细胞外捕集物的喷射。其中，组蛋白H4结合并溶解SMC，导致斑块的不稳定;相反，组蛋白H4的中和可防止SMC的细胞死亡并稳定动脉粥样硬化病变。我们的数据鉴定了通过白细胞煽动的慢性血管疾病的核心发现的细胞死亡形式，并且可以治疗靶向。

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  • 来源
    《Nature》 |2019年第7755期|236-240|共5页
  • 作者

    Silvestre-Roig Carlos; Braster Quinte; Wichapong Kanin; Lee Ernest Y.; Marie Teulon Jean; Berrebeh Nihel; Winter Janine; Adrover Jose M.; Santos Giancarlo Santiago; Froese Alexander; Lemnitzer Patricia; Ortega-Gomez Almudena; Chevre Raphael; Marschner Julian; Schumski Ariane; Winter Carla; Perez-Olivares Laura; Pan Chang; Paulin Nicole; Schoufour Tom; Hartwig Helene; Gonzalez-Ramos Silvia; Kamp Frits; Megens Remco T. A.; Mowen Kerri A.; Gunzer Matthias; Maegdefessel Lars; Hackeng Tilman; Lutgens Esther; Daemen Mat; von Blume Julia; Anders Hans-Joachim; Nikolaev Viacheslav O.; Pellequer Jean-Luc; Weber Christian; Hidalgo Andres; Nicolaes Gerry A. F.; Wong Gerard C. L.; Soehnlein Oliver;

  • 作者单位

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|AMC Dept Pathol Amsterdam Netherlands|German Ctr Cardiovasc Res DZHK Partner Site Munich Heart Alliance Munich Germany;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|AMC Dept Pathol Amsterdam Netherlands|German Ctr Cardiovasc Res DZHK Partner Site Munich Heart Alliance Munich Germany;

    Univ Maastricht Dept Biochem CARIM Maastricht Netherlands;

    Univ Calif Los Angeles Dept Bioengn Los Angeles CA USA;

    Univ Grenoble Alpes CEA CNRS IBS Grenoble France;

    Univ Grenoble Alpes CEA CNRS IBS Grenoble France;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany;

    Fdn Ctr Nacl Invest Cardiovasc Carlos III CNIC Area Dev & Cell Biol Madrid Spain;

    Univ Calif Los Angeles Dept Bioengn Los Angeles CA USA;

    Univ Med Ctr Hamburg Eppendorf Inst Expt Cardiovasc Res Hamburg Germany|German Ctr Cardiovasc Res DZHK Partner Site Hamburg Kiel Lubeck Hamburg Germany;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|German Ctr Cardiovasc Res DZHK Partner Site Munich Heart Alliance Munich Germany;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany;

    LMU Munchen Med Klin & Poliklin 4 Munich Germany;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|German Ctr Cardiovasc Res DZHK Partner Site Munich Heart Alliance Munich Germany;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|German Ctr Cardiovasc Res DZHK Partner Site Munich Heart Alliance Munich Germany;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany;

    AMC Dept Pathol Amsterdam Netherlands;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|AMC Dept Pathol Amsterdam Netherlands;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany;

    LMU Munchen BMC Metab Biochem Munich Germany;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|Univ Maastricht Dept Biomed Engn CARIM Maastricht Netherlands;

    Scripps Res Inst La Jolla CA 92037 USA;

    Univ Hosp Essen Inst Expt Immunol & Imaging Essen Germany;

    German Ctr Cardiovasc Res DZHK Partner Site Munich Heart Alliance Munich Germany|Tech Univ Munich Dept Vasc & Endovasc Surg Munich Germany|Karolinska Inst Dept Med Solna Stockholm Sweden;

    Univ Maastricht Dept Biochem CARIM Maastricht Netherlands;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|AMC Dept Med Biochem Amsterdam Netherlands;

    AMC Dept Pathol Amsterdam Netherlands;

    Max Planck Inst Biochem Martinsried Germany;

    LMU Munchen Med Klin & Poliklin 4 Munich Germany;

    Univ Med Ctr Hamburg Eppendorf Inst Expt Cardiovasc Res Hamburg Germany|German Ctr Cardiovasc Res DZHK Partner Site Hamburg Kiel Lubeck Hamburg Germany;

    Univ Grenoble Alpes CEA CNRS IBS Grenoble France;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|German Ctr Cardiovasc Res DZHK Partner Site Munich Heart Alliance Munich Germany|Univ Maastricht Dept Biochem CARIM Maastricht Netherlands;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|Fdn Ctr Nacl Invest Cardiovasc Carlos III CNIC Area Dev & Cell Biol Madrid Spain;

    Univ Maastricht Dept Biochem CARIM Maastricht Netherlands;

    Univ Calif Los Angeles Dept Bioengn Los Angeles CA USA;

    LMU Munchen Inst Cardiovasc Prevent IPEK Munich Germany|AMC Dept Pathol Amsterdam Netherlands|German Ctr Cardiovasc Res DZHK Partner Site Munich Heart Alliance Munich Germany|Karolinska Inst Dept Med Solna Stockholm Sweden|Karolinska Inst Dept Physiol & Pharmacol FyFa Stockholm Sweden;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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