Eosinophil and neutrophil extracellular DNA traps in human allergic asthmatic airways.

Eosinophil and neutrophil extracellular DNA traps in human allergic asthmatic airways.
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DOI:
10.1016/j.jaci.2010.12.1103
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发表时间:
2011-05
期刊:
The Journal of allergy and clinical immunology
影响因子:
--
通讯作者:
Yousefi S
Yousefi S
中科院分区:
其他
文献类型:
--
作者:
Dworski R;Simon HU;Hoskins A;Yousefi S

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哮喘是一种异质性气道炎症性疾病,包括嗜酸性粒细胞和非嗜酸性粒细胞表型。与正常肺不同,嗜酸性粒细胞通常存在于特应性哮喘气道中,尽管哮喘受试者的亚群主要发展嗜酸性炎症。最近,已经证明嗜酸性粒细胞和中性粒细胞产生由DNA和细胞毒性颗粒蛋白组成的杀菌性细胞外陷阱。探讨嗜酸性粒细胞和中性粒细胞浸润人特应性哮喘气道是否在体内主动形成细胞外DNA陷阱。对20例轻度特应性哮喘患者和10例正常人的支气管内活检标本进行了嗜酸性粒细胞释放DNA的定量分析。DNA用碘化丙啶染色,主要碱性蛋白(MBP)用特异性抗体染色。在支气管肺泡液中评估分类细胞计数和细胞因子/趋化因子。嗜酸性粒细胞浸润哮喘气道的数量显著高于正常气道(39.3±4.6 vs. 0.4±0.9,p<0.0001)。除了一名对照受试者外,所有哮喘患者均表达与MBP共定位的嗜酸性粒细胞释放DNA(33.65±20.33 vs.0.3 ±0.9/hpf,p<0.0001)。4例哮喘患者多为嗜中性粒细胞炎症和中性粒细胞DNA陷阱。过敏原激发对嗜酸性粒细胞或中性粒细胞DNA陷阱没有显著的定量影响。气道嗜酸性粒细胞或DNA陷阱与哮喘患者的IL-5、IFN-γ或嗜酸性粒细胞趋化因子的BAL水平或乙酰甲胆碱或过敏原的激发剂量无关。人特应性哮喘气道嗜酸性粒细胞和中性粒细胞产生细胞外DNA陷阱。这一新发现的机制和作用需要进一步研究。嗜酸性粒细胞胞外陷阱(Eosinophil extracellular traps,ESTs)(1)在特应性哮喘中常见,(2)由DNA和颗粒蛋白组成,(3)可能是反映嗜酸性粒细胞活化的一种新的有用的生物标志物。
Asthma is a heterogeneous inflammatory airway disorder which involves eosinophilic and non-eosinophilic phenotypes. Unlike in normal lungs, eosinophils are often present in atopic asthmatic airways although a subpopulation of asthmatic subjects predominantly develops neutrophilic inflammation. Recently, it has been demonstrated that eosinophils and neutrophils generate bactericidal extracellular traps consisting of DNA and cytotoxic granule proteins. To explore if living eosinophils and neutrophils infiltrating human atopic asthmatic airways actively form extracellular DNA traps in vivo. Quantitative analysis of eosinophils-releasing DNA was performed in endobronchial biopsies from 20 mild human atopic asthmatics at baseline and after local allergen challenge, and 10 normal subjects. DNA was stained with propidium iodine and major basic protein (MBP) with specific antibody. Differential cell counts and cytokines/chemokines were assessed in bronchoalveolar fluids. Asthmatic airways were infiltrated with a significantly higher number of eosinophils than normal airways (39.3±4.6 vs. 0.4±0.9, p<0.0001). All asthmatics but only one control subject expressed eosinophils releasing DNA that colocalized with MBP (33.65±20.33 vs. 0.3±0.9 per hpf, p<0.0001). Four asthmatics mostly expressed neutrophilic inflammation and neutrophil DNA traps. Allergen challenge had no significant quantitative effect on eosinophil or neutrophil DNA traps. Airway eosinophils or DNA traps did not correlate with either BAL levels of IL-5, IFN-γ, or eotaxin, or the provoking doses of methacholine or allergen in asthmatics. Extracellular DNA traps are generated by eosinophils and neutrophils in human atopic asthmatic airways in vivo. The mechanism and role of this new finding will necessitate further investigation. Eosinophil extracellular traps (EETs) (1) are frequently seen in atopic asthma, (2) consist of DNA and granule proteins, and (3) might be a new useful biomarker reflecting eosinophil activation.
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