Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature.
Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature.
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DOI：
10.1038/ncomms7673
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发表时间：
2015-03-26
影响因子：
16.6
通讯作者：
Kubes, Paul
中科院分区：
文献类型：
--
作者：
Kolaczkowska, Elzbieta;Jenne, Craig N.;Surewaard, Bas G. J.;Thanabalasuriar, Ajitha;Lee, Woo-Yong;Sanz, Maria-Jesus;Mowen, Kerri;Opdenakker, Ghislain;Kubes, Paul
由组蛋白和蛋白酶修饰的DNA组成的神经元细胞外陷阱（NETs）捕获并杀死细菌，但也损伤宿主组织。在这里，我们表明，在耐甲氧西林金黄色葡萄球菌的血流感染，大多数细菌立即被肝枯否细胞隔离，导致短暂的肝酶，局灶性缺血区和一个强大的中性粒细胞浸润到肝脏。中性粒细胞将NET释放到肝脉管系统中，其通过血管性血友病因子保持锚定到血管壁并显示显著的中性粒细胞弹性蛋白酶（NE）蛋白水解活性。重要的是，DNA酶虽然在DNA去除方面非常有效，并且在抑制NE蛋白水解活性方面有些有效，但不能从血管壁去除大部分组蛋白，并且仅部分减少损伤。相比之下，抑制NET产生（如PAD 4缺陷模型）或预防NET形成和蛋白水解活性（如NE−/−小鼠模型）可预防附带宿主组织损伤。 由中性粒细胞释放的中性粒细胞胞外陷阱（NET）捕获病原体，但也可能导致组织损伤。在这里，作者表明，在全身性金黄色葡萄球菌感染期间，锚定到脉管系统的NET仅部分对DNA酶敏感，提倡更好的抗NET治疗。
Neutrophil extracellular traps (NETs) composed of DNA decorated with histones and proteases trap and kill bacteria but also injure host tissue. Here we show that during a bloodstream infection with methicillin-resistant Staphylococcus aureus, the majority of bacteria are sequestered immediately by hepatic Kupffer cells, resulting in transient increases in liver enzymes, focal ischaemic areas and a robust neutrophil infiltration into the liver. The neutrophils release NETs into the liver vasculature, which remain anchored to the vascular wall via von Willebrand factor and reveal significant neutrophil elastase (NE) proteolytic activity. Importantly, DNase although very effective at DNA removal, and somewhat effective at inhibiting NE proteolytic activity, fails to remove the majority of histones from the vessel wall and only partly reduces injury. By contrast, inhibition of NET production as modelled by PAD4-deficiency, or prevention of NET formation and proteolytic activity as modelled in NE−/− mice prevent collateral host tissue damage. Neutrophil extracellular traps (NETs) released by neutrophils trap pathogens but may also cause tissue damage. Here the authors show that during systemic Staphylococcus aureus infection NETs anchoring to the vasculature are only partially DNase-sensitive, advocating for better anti-NET therapies.
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组蛋白的杀菌作用。
影响因子：
15.3
作者：
HIRSCH, J G
通讯作者：
HIRSCH, J G
DOI：
10.1038/nri3552
发表时间：
2013-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
28.2
作者：
Kaasch, Achim J.;Barlow, Gavin;Edgeworth, Jonathan D.;Fowler, Vance G.;Hellmich, Martin;Hopkins, Susan;Kern, Winfried V.;Llewelyn, Martin J.;Rieg, Siegbert;Rodriguez-Bano, Jesus;Scarborough, Matthew;Seifert, Harald;Soriano, Alex;Tilley, Robert;Torok, M. Estee;Weiss, Verena;Wilson, A. Peter R.;Thwaites, Guy E.
通讯作者：
Thwaites, Guy E.
DOI：
10.1152/ajpregu.90346.2008
发表时间：
2008-10-01
影响因子：
2.8
作者：
Jun, Jonathan;Savransky, Vladimir;Polotsky, Vsevolod Y.
通讯作者：
Polotsky, Vsevolod Y.
DOI：
10.1165/rcmb.2011-0380oc
发表时间：
2012-07-01
影响因子：
6.4
作者：
Dubois, Alice V.;Gauthier, Alexandre;Attucci, Sylvie
通讯作者：
Attucci, Sylvie