气道巨噬细胞中的嗜酸性粒细胞蛋白：哮喘患者嗜酸性炎症的新型生物标志物。
Eosinophil protein in airway macrophages: a novel biomarker of eosinophilic inflammation in patients with asthma.
机构信息
Institute for Lung Health, Glenfield Hospital, Leicester, and the Department of Infection, Immunity and Inflammation, University of Leicester, United Kingdom.
Children's Community Health Service, Leicester City NHS Primary Care Trust.
出版信息
J Allergy Clin Immunol. 2010 Jul;126(1):61-9.e3. doi: 10.1016/j.jaci.2010.03.026.
BACKGROUND
Noneosinophilic asthma is common across asthma severities. However, in patients with moderate-to-severe disease, the absence of sputum eosinophilia cannot distinguish between asthmatic subjects with eosinophilic inflammation controlled by corticosteroids versus those in whom eosinophilic inflammation is not a component of the disease.
OBJECTIVES
We sought to develop a method to quantify eosinophil proteins in airway macrophages as a novel biomarker of eosinophilic airway inflammation.
METHODS
Eosinophil proteins in airway macrophages were assessed by means of flow cytometry, immunofluorescence, and cytoplasmic hue change after ingestion of apoptotic eosinophils. Airway macrophage median percentage of red-hued area in stained sputum cytospin preparations was assessed by means of image analysis from (1) subjects with mild-to-severe asthma, subjects with nonasthmatic eosinophilic bronchitis, and healthy control subjects; (2) subjects with eosinophilic severe asthma after treatment with prednisolone; and (3) subject with noneosinophilic asthma before corticosteroid withdrawal.
RESULTS
Eosinophil proteins were detected in airway macrophages, and cytoplasmic red hue increased after ingestion of apoptotic eosinophils. Airway macrophage percentage redhued area was increased in subjects with moderate-to-severe asthma compared with that seen in subjects with mild asthma and healthy control subjects, was similar in those with or without a sputum eosinophilia, and was increased after corticosteroid therapy. In asthmatic subjects without sputum eosinophilia, the airway macrophage percentage red-hued area was increased in subjects who did versus those who did not have sputum eosinophilia after corticosteroid withdrawal.
CONCLUSIONS
Eosinophil proteins can be reliably measured in airway macrophages. In combination with sputum eosinophilia, the macrophage eosinophil protein content might further define the asthma phenotype and provide an additional tool to direct therapy.
背景
非嗜酸性粒细胞性哮喘在各严重程度哮喘中均常见。然而，在中重度疾病患者中，痰嗜酸性粒细胞缺乏不能区分糖皮质激素控制下的嗜酸性粒细胞性炎症的哮喘患者与疾病中无嗜酸性粒细胞炎症的哮喘患者。
目的
我们试图开发一种方法来定量气道巨噬细胞中的嗜酸性粒细胞蛋白，作为一种新型的嗜酸性气道炎症的生物标志物。
方法
通过流式细胞术、免疫荧光和吞噬凋亡嗜酸性粒细胞后的细胞质色调变化来评估气道巨噬细胞中的嗜酸性粒细胞蛋白。通过对染色痰细胞涂片的图像分析来评估气道巨噬细胞在染色痰细胞涂片上的红色区域中位数百分比，该分析包括：（1）轻度至重度哮喘患者、非哮喘性嗜酸性粒细胞性支气管炎患者和健康对照者；（2）接受泼尼松龙治疗后的嗜酸性粒细胞性严重哮喘患者；（3）在停用皮质类固醇前的非嗜酸性粒细胞性哮喘患者。
结果
在气道巨噬细胞中检测到嗜酸性粒细胞蛋白，吞噬凋亡嗜酸性粒细胞后细胞质红色色调增加。与轻度哮喘患者和健康对照者相比，中重度哮喘患者的气道巨噬细胞红色区域百分比增加，无论是否有痰嗜酸性粒细胞，其百分比均相似，且在皮质类固醇治疗后增加。在无痰嗜酸性粒细胞的哮喘患者中，在停用皮质类固醇后，气道巨噬细胞红色区域百分比增加的患者与无痰嗜酸性粒细胞患者相比。
结论
气道巨噬细胞中的嗜酸性粒细胞蛋白可以可靠地测量。与痰嗜酸性粒细胞结合，巨噬细胞嗜酸性粒细胞蛋白含量可能进一步定义哮喘表型，并提供指导治疗的额外工具。
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