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Eosinophil activation and novel mediators in the aspirin-induced nasal response in AERD

机译：阿司匹林引起的鼻腔反应中嗜酸性粒细胞激活和新型介体

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Background: Eosinophil activation is the key feature of upper and lower airway inflammation in aspirin-exacerbated respiratory disease (AERD). Objective: To investigate the mechanism of eosinophil activation and identify novel inflammatory mediators using proteomics. Methods: Thirty-two asthmatic subjects were enrolled: 18 AERD patients who showed positive responses to the lysine-aspirin nasal provocation test (L-ASA NPT) and 14 aspirin-tolerant asthma (ATA) patients who showed negative responses to the L-ASA NPT (control group). Nasal lavage fluid (NLF) was collected before (baseline), at 10, 30 and 60 min (early response), and at 3 h (late response) after the L-ASA NPT. Eosinophil cationic protein (ECP) and cysteinyl leucotriene (CysLT) levels were measured using an ImmunoCAP system and ELISA respectively. To identify proteins involved in AERD, comparative proteomics was applied using NLFs collected before and after L-ASA NPTs in AERD patients. The clinical relevance of identified novel proteins was evaluated by ELISA using NLFs from the AERD and ATA groups. Results: Eosinophil cationic protein and CysLT levels both increased significantly during the early response in AERD. ECP levels increased until the late response in AERD, while CysLT levels were not significantly increased during the late response. Proteomic analysis showed up-regulation of apolipoprotein A1 (ApoA1), α2-macroglobulin (α2M) and ceruloplasmin (CP), with significant increases in NLF of AERD patients, which was significantly higher in AERD patients with chronic rhinosinusitis. Significant correlations were noted between ECP and CysLT, ApoA1, α2M and CP levels during the early response in AERD patients. Conclusion: Eosinophil activation occurred in early and late responses after L-ASA NPT in upper airway mucosa of AERD patients, where ApoA1, α2M and CP as well as CysLT may be involved in eosinophilic inflammation.
机译：背景：嗜酸性粒细胞激活是阿司匹林加重呼吸道疾病（AERD）中上，下呼吸道炎症的关键特征。目的：探讨嗜酸性粒细胞活化的机制，并利用蛋白质组学方法鉴定新型炎症介质。方法：招募了32名哮喘受试者：18名AERD患者对赖氨酸阿司匹林鼻腔激发试验（L-ASA NPT）呈阳性反应，以及14名阿司匹林耐受性哮喘（ATA）对L-ASA阴性的患者NPT（对照组）。在L-ASA NPT之前（基线），10、30和60分钟（早期反应）和3小时（晚期反应）收集鼻灌洗液（NLF）。分别使用ImmunoCAP系统和ELISA检测嗜酸性粒细胞阳离子蛋白（ECP）和半胱氨酰白三烯（CysLT）的水平。为了鉴定参与AERD的蛋白质，使用在AERD患者中L-ASA NPT之前和之后收集的NLF进行比较蛋白质组学。使用AERD和ATA组的NLF，通过ELISA评估鉴定出的新蛋白的临床相关性。结果：AERD早期应答期间，嗜酸性粒细胞阳离子蛋白和CysLT水平均显着增加。 ECP的水平一直升高到AERD的晚期应答为止，而CysLT的水平在晚期应答期间并未明显升高。蛋白质组学分析显示，载脂蛋白A1（ApoA1），α2-巨球蛋白（α2M）和铜蓝蛋白（CP）上调，而AERD患者的NLF明显升高，在慢性鼻-鼻窦炎的AERD患者中明显升高。在AERD患者的早期反应期间，ECP与CysLT，ApoA1，α2M和CP水平之间存在显着相关性。结论：AERD患者上呼吸道黏膜L-ASA NPT后早期和晚期反应中都发生嗜酸性粒细胞活化，其中ApoA1，α2M和CP以及CysLT可能与嗜酸性粒细胞炎症有关。

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