Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones.
Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones.
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DOI：
10.1371/journal.pone.0032366
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Preissner KT
中科院分区：
文献类型：
--
作者：
Saffarzadeh M;Juenemann C;Queisser MA;Lochnit G;Barreto G;Galuska SP;Lohmeyer J;Preissner KT
中性粒细胞通过保护宿主生物体免受入侵微生物的侵害而在先天免疫中发挥重要作用。中性粒细胞的抗菌活性是通过释放抗菌肽、吞噬作用以及形成中性粒细胞胞外陷阱（NET）来介导的。这些结构由DNA、组蛋白和颗粒蛋白如中性粒细胞弹性蛋白酶和髓过氧化物酶组成。本研究着重于NET对宿主细胞功能的影响，特别是对人肺泡上皮细胞作为肺中负责气体交换的主要细胞的影响。在与上皮细胞和内皮细胞直接相互作用后，NET以剂量依赖性方式诱导细胞毒性效应，NET中DNA的消化不改变NET介导的细胞毒性。NET与抗组蛋白抗体、聚唾液酸或髓过氧化物酶抑制剂（但不与弹性蛋白酶抑制剂）的预孵育降低了NET介导的细胞毒性，表明组蛋白和髓过氧化物酶是NET介导的细胞毒性的原因。虽然活化蛋白C（APC）确实降低了纯化系统中组蛋白诱导的细胞毒性，但它并没有改变NET诱导的细胞毒性，表明NET的组蛋白依赖性细胞毒性受到APC降解的保护。此外，在LPS诱导的急性肺损伤小鼠模型中，在肺组织以及支气管肺泡灌洗液中记录了NET形成。这些数据揭示了NET中蛋白质组分的重要作用，特别是组蛋白，其可能导致宿主细胞毒性并可能参与肺组织破坏。
Neutrophils play an important role in innate immunity by defending the host organism against invading microorganisms. Antimicrobial activity of neutrophils is mediated by release of antimicrobial peptides, phagocytosis as well as formation of neutrophil extracellular traps (NET). These structures are composed of DNA, histones and granular proteins such as neutrophil elastase and myeloperoxidase. This study focused on the influence of NET on the host cell functions, particularly on human alveolar epithelial cells as the major cells responsible for gas exchange in the lung. Upon direct interaction with epithelial and endothelial cells, NET induced cytotoxic effects in a dose-dependent manner, and digestion of DNA in NET did not change NET-mediated cytotoxicity. Pre-incubation of NET with antibodies against histones, with polysialic acid or with myeloperoxidase inhibitor but not with elastase inhibitor reduced NET-mediated cytotoxicity, suggesting that histones and myeloperoxidase are responsible for NET-mediated cytotoxicity. Although activated protein C (APC) did decrease the histone-induced cytotoxicity in a purified system, it did not change NET-induced cytotoxicity, indicating that histone-dependent cytotoxicity of NET is protected against APC degradation. Moreover, in LPS-induced acute lung injury mouse model, NET formation was documented in the lung tissue as well as in the bronchoalveolar lavage fluid. These data reveal the important role of protein components in NET, particularly histones, which may lead to host cell cytotoxicity and may be involved in lung tissue destruction.
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DOI：
10.1152/ajplung.00275.2003
发表时间：
2004-04-01
影响因子：
4.9
作者：
Bozinovski, S;Jones, J;Anderson, GP
通讯作者：
Anderson, GP
影响因子：
24.3
作者：
Faffe, DS;Seidl, VR;Zin, WA
通讯作者：
Zin, WA
影响因子：
2.7
作者：
Gupta, AK;Hasler, P;Hahn, S
通讯作者：
Hahn, S
DOI：
10.1073/pnas.0900226106
发表时间：
2009-04-21
影响因子：
11.1
作者：
Guimaraes-Costa, Anderson B.;Nascimento, Michelle T. C.;Saraiva, Elvira M.
通讯作者：
Saraiva, Elvira M.
影响因子：
11.5
作者：
Bergmann, Christoph;Strauss, Laura;Whiteside, Theresa L.
通讯作者：
Whiteside, Theresa L.