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中性粒细胞胞外诱捕网(NETs)——形成及其影响

Neutrophil extracellular traps (NETs) - formation and implications.

作者信息

Zawrotniak Marcin, Rapala-Kozik Maria

机构信息

Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.

出版信息

Acta Biochim Pol. 2013;60(3):277-84. Epub 2013 Jul 1.

Abstract

Neutrophils are cells of the immune system which freely circulate in blood vessels and are recruited to the inflammation sites when the human organism responds to microbial infections. One of the mechanisms of neutrophil action is the formation of neutrophil extracellular traps (NETs) The process of NET generation, called netosis, is a specific type of cell death, different from necrosis and apoptosis. NETs are formed by neutrophils upon contact with various bacteria or fungi as well as with activated platelets or under the influence of numerous inflammatory stimuli, and this process is associated with dramatic changes in the morphology of the cells. The main components of NETs, DNA and granular antimicrobial proteins, determine their antimicrobial properties. The pathogens trapped in NETs are killed by oxidative and non-oxidative mechanisms. On the other hand, it was also discovered that chromatin and proteases released into the circulatory system during NET formation can regulate procoagulant and prothrombotic factors and take part in clot formation in blood vessels. NETs have also been detected in lungs where they are involved in chronic inflammation processes in ALI/ARDS patients. Moreover, DNA-proteins complexes have been found in the airway fluids of cystic fibrosis patients where they can increase the viscosity of the sputum and have a negative impact on the lung functions. The DNA-complexed granular proteins and other proteins released by neutrophils during netosis lead to autoimmunity syndromes such as systemic lupus erythematosus (SLE), small-vessel vasculitis (SVV) or autoimmune diseases associated with the formation of autoantibodies against chromatin and neutrophil components. A possible involvement of NETs in metastasis is also considered.

摘要

中性粒细胞是免疫系统的细胞,它们在血管中自由循环,当人体对微生物感染作出反应时,会被招募到炎症部位。中性粒细胞作用的机制之一是形成中性粒细胞胞外陷阱(NETs)。NET生成的过程,称为NETosis,是一种特定类型的细胞死亡,不同于坏死和凋亡。NETs由中性粒细胞在与各种细菌或真菌接触时、与活化的血小板接触时或在多种炎症刺激的影响下形成,这个过程与细胞形态的显著变化有关。NETs的主要成分,DNA和颗粒状抗菌蛋白,决定了它们的抗菌特性。被困在NETs中的病原体通过氧化和非氧化机制被杀死。另一方面,人们还发现,在NET形成过程中释放到循环系统中的染色质和蛋白酶可以调节促凝血和血栓形成因子,并参与血管内的凝血过程。在肺部也检测到了NETs,它们参与了急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)患者的慢性炎症过程。此外,在囊性纤维化患者的气道分泌物中发现了DNA-蛋白质复合物,它们会增加痰液的粘度,并对肺功能产生负面影响。中性粒细胞在NETosis过程中释放的DNA复合颗粒蛋白和其他蛋白质会导致自身免疫综合征,如系统性红斑狼疮(SLE)、小血管血管炎(SVV)或与针对染色质和中性粒细胞成分的自身抗体形成相关的自身免疫疾病。人们还考虑了NETs可能参与转移的情况。

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