Characterization of macrophage activation states in patients with cystic fibrosis
Characterization of macrophage activation states in patients with cystic fibrosis
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DOI：
10.1016/j.jcf.2010.04.006
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发表时间：
2010-09-01
影响因子：
5.2
通讯作者：
Feola, David J.
中科院分区：
文献类型：
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作者：
Murphy, Brian S.;Bush, Heather M.;Feola, David J.
背景：慢性气道炎症是囊性纤维化（CF）患者的特征。替代性巨噬细胞激活在此病程中的作用尚不清楚。 目的：我们评估了 CF 患者肺部替代性和经典巨噬细胞激活的标志物，并在铜绿假单胞菌 (PA) 感染、免疫调节药物治疗和肺功能的背景下评估了这些特征。 方法：收集了 48 名 CF 患者的支气管肺泡灌洗或自发咳出的痰样本。临床数据与甘露糖受体 (MR)（在替代激活的巨噬细胞中上调）和 TLR4（在经典激活的巨噬细胞中上调）的巨噬细胞表面表达相关。此外，还比较了患者组之间替代激活的巨噬细胞效应分子精氨酸酶的活性，并测量了替代激活的巨噬细胞和经典激活的巨噬细胞产生的促炎和抗炎细胞因子。 结果：PA感染和未感染的患者在多项临床测量中存在显着差异。 PA 感染患者表现出阿奇霉素使用增加、CD11b+ 细胞上 MR 上调以及肺样本中精氨酸酶活性增加，并且 MR 和精氨酸酶活性与 FEV1 之间存在很强的负相关关系 (1)。经过进一步分析，接受阿奇霉素治疗的 PA 感染患者具有最高的精氨酸酶活性和最多的 MR+TLR4- 巨噬细胞数量，并且这两个标志物均与 FEV1 呈负相关。 结论：我们的研究结果表明，在患有 CF 的 PA 感染患者中，随着肺功能下降，MR 和精氨酸酶表达均增加。这些替代性活化巨噬细胞表型的标记为未来研究确定 CF (C) 2010 欧洲囊性纤维化协会中巨噬细胞活化状态的功能提供了依据。由 Elsevier B.V. 出版。保留所有权利。
Background: Chronic airway inflammation characterizes patients with cystic fibrosis (CF). The role of alternative macrophage activation in this disease course is unknown.Objective: We evaluated markers of alternative and classical macrophage activation in the lungs of patients with CF and evaluated these characteristics in the context of Pseudomonas aeruginosa (PA) infection, immunomodulatory drug therapy and pulmonary function.Methods: Bronchoalveolar lavage or spontaneously expectorated sputum samples were collected from 48 CF patients. Clinical data were related to macrophage surface expression of mannose receptor (MR) (up-regulated in alternatively activated macrophages) and TLR4 (up-regulated in classically activated macrophages). Also, the activity of the alternatively activated macrophage effector molecule arginase was compared among patient groups, and pro- and anti-inflammatory cytokines produced by alternatively and classically activated macrophages were measured.Results: There were significant differences between PA-infected and -uninfected patients in several clinical measurements. PA-infected patients exhibited increased use of azithromycin, up-regulation of MR on CD11b+ cells and increased arginase activity in their lung samples, and had a strong inverse relationship between MR and arginase activity to FEV(1). Upon further analysis, PA-infected patients who were treated with azithromycin had the highest arginase activity and the highest number of macrophages that were MR+TLR4-, and both of these markers were inversely related to the FEV(1).Conclusions: Our findings suggest an increase in both MR and arginase expression as pulmonary function declines in PA-infected patients with CF. These markers of an alternatively activated macrophage phenotype give cause for future study to define the function of macrophage activation states in the CF (C) 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.