Biological function of eosinophil extracellular traps in patients with severe eosinophilic asthma.
Biological function of eosinophil extracellular traps in patients with severe eosinophilic asthma.
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DOI：
10.1038/s12276-018-0136-8
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发表时间：
2018-08-16
影响因子：
12.8
通讯作者：
Park HS
中科院分区：
文献类型：
--
作者：
Choi Y;Le Pham D;Lee DH;Lee SH;Kim SH;Park HS
嗜酸性粒细胞胞外陷阱（Escherichia coli extracellular traps，Escherichia coli）是一种DNA纤维和细胞毒性颗粒蛋白的复合物，与哮喘的发生有关;然而，Escherichia coli在免疫应答中的病理生理功能尚未完全确定。本研究对20例非重度哮喘（NSA）和20例重度嗜酸性粒细胞性哮喘（SEA）患者的EET特征进行了研究，并对EET功能进行了评价。SEA患者经IL-5和LPS刺激形成EET的外周血嗜酸性粒细胞百分比显著高于NSA患者（P = 0.009）。该百分比与基线FEV 1呈负相关（r =-0.350，P = 0.027），与哮喘受试者血清嗜酸性粒细胞源性神经毒素水平呈正相关（r = 0.437，P = 0.018）。EET的形成与活性氧的产生有显著相关性（r = 0.750，P < 0.001）。这些嗜酸性粒细胞表现出自分泌功能，诱导嗜酸性粒细胞脱粒，从而导致颗粒蛋白的产生。气道上皮细胞刺激与Eclampin表现出增加上皮脱落和渗透性和促炎细胞因子释放。然而，EAE与肥大细胞活化无显著相关性。目前的研究表明，SEA患者的外周血嗜酸性粒细胞可能比NSA患者的嗜酸性粒细胞更活化，从而产生EkB，这进一步诱导哮喘气道的炎症。因此，调节EET的形成和功能可能是哮喘管理的一种新的治疗方法。控制诱导哮喘气道损伤的DNA和蛋白质的网状结构的形成可以提供新的治疗机会，特别是对于那些对常规治疗反应不佳的患者。这些结构是由激活的细胞产生的，作为哮喘免疫反应的一部分。它们被称为嗜酸性粒细胞细胞外陷阱（Escherichia coli，Escherichia coli），因为它们最显著地由称为嗜酸性粒细胞的白色血细胞的活动释放。韩国Ajou大学的Hae-Sim Park及其同事研究了Escherichia coli与严重哮喘患者的关系。他们的研究结果表明，严重哮喘患者的嗜酸性粒细胞比那些病情较轻的患者更容易被激活，产生破坏性的Ehrs。寻找控制EET形成的方法可能是帮助严重嗜酸性粒细胞性哮喘患者的有效方法。
Eosinophil extracellular traps (EETs), a complex of DNA fibers and cytotoxic granule proteins, are implicated in the development of asthma; however, the pathophysiological function of EETs in immune responses has not been fully determined. The present study investigated the characteristics of EETs from patients with non-severe asthma (NSA, n = 20) and severe eosinophilic asthma (SEA, n = 20) and evaluated EET function. The percentage of EET-forming peripheral blood eosinophils stimulated with IL-5 and LPS was significantly higher in patients with SEA than in those with NSA (P = 0.009). This percentage negatively correlated with baseline FEV1 (r = −0.350, P = 0.027) and positively correlated with serum eosinophil-derived neurotoxin levels in asthmatic subjects (r = 0.437, P = 0.018). In addition, EET formation was markedly associated with reactive oxygen species production (r = 0.750, P < 0.001). These EETs exhibited an autocrine function to induce eosinophil degranulation, which led to granule protein production. Airway epithelial cells stimulated with EETs exhibited increased epithelial detachment and permeability and pro-inflammatory cytokine release. However, EETs were not significantly associated with mast cell activation. The present study suggests that peripheral blood eosinophils from patients with SEA may be more activated to produce EETs than those from patients with NSA, which further induces inflammation in asthmatic airways. Therefore, regulation of EET formation and function may be a novel therapeutic approach for asthma management. Controlling the formation of mesh-like structures of DNA and protein which induce airway damage in asthma could offer new therapeutic opportunities, especially for patients who do not respond well to conventional treatments. The structures are produced by activated cells as part of the immune response in asthma. They are known as eosinophil extracellular traps (EETs) since they are most prominently released by the activity of white blood cells called eosinophils. Hae-Sim Park and colleagues at Ajou University in South Korea studied the involvement of EETs in patients with severe asthma. Their results suggest eosinophils are more activated to create damaging EETs in patients with severe asthma than in those with less severe forms of the disease. Searching for ways to control EET formation could be a fruitful approach to helping patients with severe eosinophilic asthma.