Department of Internal Medicine, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA.
J Cyst Fibros. 2010 Sep;9(5):314-22. doi: 10.1016/j.jcf.2010.04.006. Epub 2010 Jun 8.
Chronic airway inflammation characterizes patients with cystic fibrosis (CF). The role of alternative macrophage activation in this disease course is unknown.
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.
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.
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).
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 lung.
慢性气道炎症是囊性纤维化（CF）患者的特征。替代型巨噬细胞激活在该病病程中的作用尚不清楚。
我们评估了 CF 患者肺部的替代型和经典型巨噬细胞激活标志物，并评估了这些特征在铜绿假单胞菌（PA）感染、免疫调节药物治疗和肺功能中的情况。
从 48 例 CF 患者中收集支气管肺泡灌洗液或自发咳出的痰液样本。临床数据与巨噬细胞表面甘露糖受体（MR）（在替代型激活的巨噬细胞中上调）和 TLR4（在经典型激活的巨噬细胞中上调）的表达有关。此外，还比较了患者组之间替代型激活的巨噬细胞效应分子精氨酸酶的活性，并测量了替代型和经典型激活的巨噬细胞产生的促炎和抗炎细胞因子。
PA 感染和未感染患者在多个临床指标上存在显著差异。PA 感染患者表现出更高的阿奇霉素使用率、CD11b+细胞上 MR 的上调以及其肺部样本中精氨酸酶活性的增加，并且 MR 和精氨酸酶活性与 FEV1 呈强负相关。进一步分析显示，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，这两个标志物均与 FEV1 呈负相关。
我们的研究结果表明，在 CF 合并 PA 感染患者中，随着肺功能下降，MR 和精氨酸酶的表达均增加。这些替代型激活的巨噬细胞表型标志物提示，未来需要进一步研究来确定巨噬细胞激活状态在 CF 肺部中的功能。
