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嗜酸性粒细胞胞外 DNA 陷阱:分子机制及其在疾病中的潜在作用。

Eosinophil extracellular DNA traps: molecular mechanisms and potential roles in disease.

机构信息

Institute of Pharmacology, University of Bern, Bern, Switzerland.

出版信息

Curr Opin Immunol. 2012 Dec;24(6):736-9. doi: 10.1016/j.coi.2012.08.010. Epub 2012 Sep 13.

Abstract

Eosinophil extracellular traps (EETs) are part of the innate immune response and are seen in multiple infectious, allergic, and autoimmune eosinophilic diseases. EETs are composed of a meshwork of DNA fibers and eosinophil granule proteins, such as major basic protein (MBP) and eosinophil cationic protein (ECP). Interestingly, the DNA within the EETs appears to have its origin in the mitochondria of eosinophils, which had released most their mitochondrial DNA, but were still viable, exhibiting no evidence of a reduced life span. Multiple eosinophil activation mechanisms are represented, whereby toll-like, cytokine, chemokine, and adhesion receptors can all initiate transmembrane signal transduction processes leading to the formation of EETs. One of the key signaling events required for DNA release is the activation of the NADPH oxidase. Here, we review recent progress made in the understanding the molecular mechanisms involved in DNA and granule protein release, discuss the presence of EETs in disease, speculate on their potential role(s) in pathogenesis, and compare available data on other DNA-releasing cells, particularly neutrophils.

摘要

嗜酸性粒细胞外诱捕网 (EETs) 是先天免疫反应的一部分,可见于多种感染性、过敏性和自身免疫性嗜酸性粒细胞疾病中。EETs 由 DNA 纤维和嗜酸性粒细胞颗粒蛋白(如主要碱性蛋白 [MBP] 和嗜酸性粒细胞阳离子蛋白 [ECP])组成的网状结构构成。有趣的是,EETs 中的 DNA 似乎源自嗜酸性粒细胞的线粒体,这些线粒体已经释放了大部分线粒体 DNA,但仍然存活,没有证据表明寿命缩短。多种嗜酸性粒细胞激活机制被认为可以启动跨膜信号转导过程,导致 EETs 的形成。其中一个需要 DNA 释放的关键信号事件是 NADPH 氧化酶的激活。在这里,我们回顾了在理解涉及 DNA 和颗粒蛋白释放的分子机制方面取得的最新进展,讨论了 EETs 在疾病中的存在,推测了它们在发病机制中的潜在作用,并比较了其他 DNA 释放细胞(特别是中性粒细胞)的可用数据。

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