NETosis and NADPH oxidase: at the intersection of host defense, inflammation, and injury.
NETosis and NADPH oxidase: at the intersection of host defense, inflammation, and injury.
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DOI：
10.3389/fimmu.2013.00045
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发表时间：
2013
影响因子：
7.3
通讯作者：
Segal BH
中科院分区：
文献类型：
--
作者：
Almyroudis NG;Grimm MJ;Davidson BA;Röhm M;Urban CF;Segal BH
嗜中性粒细胞具有氧化剂依赖性和非氧化剂依赖性两种途径来杀死病原体。吞噬细胞烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶的激活构成了对感染威胁的紧急反应，并导致产生抗微生物反应性氧化剂。此外，中性粒细胞中的NADPH氧化酶活化与颗粒蛋白酶的活化和中性粒细胞胞外陷阱（NET）的产生有关。NETosis涉及可以靶向细胞外病原体的核和颗粒组分的释放。NETosis在微生物威胁期间和在某些模拟脓毒症的条件下被激活，并且可以导致增强的宿主防御和炎性损伤。相反，细胞凋亡，中性粒细胞死亡的生理形式，不仅导致非炎性细胞死亡，而且有助于减轻炎症。虽然有显着的差距，知识的具体贡献NET的主机防御，我们推测，协调激活NADPH氧化酶和NETosis最大限度地杀死微生物。在工程小鼠中的工作和有限的患者经验表明，细菌和真菌病原体对NADPH氧化酶与NET组分的敏感性不同。由于反应性氧化剂和NET成分可以损伤宿主组织，因此严格调节这些途径非常重要。最近的工作支持NETosis在急性肺损伤和自身免疫中的作用。关于调节NETosis的机制的知识可能会导致新的治疗方法来限制炎症相关的损伤。
Neutrophils are armed with both oxidant-dependent and -independent pathways for killing pathogens. Activation of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase constitutes an emergency response to infectious threat and results in the generation of antimicrobial reactive oxidants. In addition, NADPH oxidase activation in neutrophils is linked to activation of granular proteases and generation of neutrophil extracellular traps (NETs). NETosis involves the release of nuclear and granular components that can target extracellular pathogens. NETosis is activated during microbial threat and in certain conditions mimicking sepsis, and can result in both augmented host defense and inflammatory injury. In contrast, apoptosis, the physiological form of neutrophil death, not only leads to non-inflammatory cell death but also contributes to alleviate inflammation. Although there are significant gaps in knowledge regarding the specific contribution of NETs to host defense, we speculate that the coordinated activation of NADPH oxidase and NETosis maximizes microbial killing. Work in engineered mice and limited patient experience point to varying susceptibility of bacterial and fungal pathogens to NADPH oxidase versus NET constituents. Since reactive oxidants and NET constituents can injure host tissue, it is important that these pathways be tightly regulated. Recent work supports a role for NETosis in both acute lung injury and in autoimmunity. Knowledge gained about mechanisms that modulate NETosis may lead to novel therapeutic approaches to limit inflammation-associated injury.
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影响因子：
8
作者：
Almuneef, M;Al Khenaizan, S;Al-Anazi, A
通讯作者：
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DOI：
10.1084/jem.20070494
发表时间：
2007-08-06
期刊：
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DOI：
10.1073/pnas.1110358108
发表时间：
2011-08-09
影响因子：
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影响因子：
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作者：
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