Elevation of S100 calcium binding protein A9 in sputum of neutrophilic inflammation in severe uncontrolled asthma
Elevation of S100 calcium binding protein A9 in sputum of neutrophilic inflammation in severe uncontrolled asthma
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DOI：
10.1016/j.anai.2013.06.028
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发表时间：
2013-10-01
影响因子：
5.9
通讯作者：
Park, Choon-Sik
中科院分区：
文献类型：
--
作者：
Lee, Tae-Hyeong;Jang, An-Soo;Park, Choon-Sik
背景：嗜中性粒细胞气道炎症在严重的未控制的哮喘（UA）和控制的哮喘（CA）中常见。然而，有没有痰生物标志物区分2 conditions.Objective：为了确定严重的不受控制的哮喘与嗜中性粒细胞的气道inflammation.Methods：痰与中性粒细胞含量大于70%的生物标志物合并从5例严重UA和10例CA患者。采用双向电泳技术进行差异显示蛋白质组学研究，并采用基质辅助激光吸附/电离飞行时间质谱技术对候选蛋白进行鉴定。采用Western blot法鉴定S100钙结合蛋白A9（S100 A9），并采用酶联免疫吸附试验（ELISA）检测不同病情的哮喘患者、慢性阻塞性肺疾病患者和正常对照者痰液中S100 A9的水平。基质辅助激光吸附/电离飞行时间/这些斑点的飞行时间显示，与CA患者相比，UA患者的人中性粒细胞肽-2，S100 A9，b-淀粉酶，中性粒细胞明胶酶相关脂质运载蛋白，4-氨基丁酸转氨酶和胱抑素SA增加。plunc前体、补体C3组分、免疫球蛋白重链可变区、胶质细胞酸性蛋白亚型-1、IgM kIIIb SON、MLL-AF 4 der（11）融合蛋白、细胞角蛋白-8和重组IgG 4重链减少。S100 A9在来自重度UA与CA患者的嗜酸性痰的蛋白质印迹中以更高的水平被检测到。S100 A9水平显着增加，酶联免疫吸附试验测定，在嗜酸性UA与CA相比，嗜酸性UA和CA，慢性阻塞性肺diseas.Conclusion：痰中S100 A9可能是一个生物标志物的嗜酸性炎症严重UA。(C)2013年美国过敏，哮喘和免疫学学院。爱思唯尔公司出版All rights reserved.
Background: Neutrophilic airway inflammation is frequently observed in severe uncontrolled asthma (UA) and controlled asthma (CA). However, there is no sputum biomarker to differentiate the 2 conditions.Objective: To identify biomarkers of severe uncontrolled asthma with neutrophilic airway inflammation.Methods: Sputum with a neutrophil content larger than 70% was pooled from 5 patients with severe UA and from 10 patients with CA. Two-dimensional electrophoresis was adopted for differential display proteomics, and candidate proteins were identified using matrix-assisted laser adsorption/ionization-time of flight mass spectrometric analysis. S100 calcium binding protein A9 (S100A9) was identified by western blot and its level was measured in sputum from asthmatics with varying disease severity, patients with chronic obstructive lung disease, and normal controls using enzyme-linked immunosorbent assay.Results: Fourteen protein spots exhibited differences in relative intensity between patients with severe UA and those with CA. Matrix-assisted laser adsorption/ionizationetime of flight/time of flight of these spots showed an increase in human neutrophil peptide-2, S100A9, b-amylase, neutrophil gelatinase-associated lipocalin, 4-aminobutyrate transaminase, and cystatin SA in patients with UA compared with patients with CA. There was a decrease in the plunc precursor, complement C3 component, immunoglobulin heavychain variable region, glial fibrillary acidic protein isoform-1, IgM kIIIb SON, MLL-AF4 der(11) fusion protein, cytokeratin-8, and recombinant IgG4 heavy chain. S100A9 was detected at a higher level in western blots of neutrophilic sputum from patients with severe UA vs CA. S100A9 levels were significantly increased, as measured by enzyme-linked immunosorbent assay, in neutrophilic UA compared with CA, eosinophilic UA and CA, and chronic obstructive lung disease.Conclusion: S100A9 in sputum may be a biomarker of neutrophilic inflammation in severe UA. (C) 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.