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气道巨噬细胞中的黑碳含量与慢性阻塞性肺疾病(COPD)既往吸烟者的CD80表达降低及病情加重增加有关。

Black Carbon Content in Airway Macrophages is Associated with Reduced CD80 Expression and Increased Exacerbations in Former Smokers With COPD.

作者信息

Tejwani Vickram, Moughames Eric, Suresh Karthik, Tang Shih-En, Mair Laura G, Romero Karina, Putcha Nirupama, Alexis Neil E, Woo Han, D'Alessio Franco R, Hansel Nadia N

机构信息

Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, Baltimore, Maryland, United States.

Johns Hopkins Bayview Medical Center, Baltimore, Maryland, United States.

出版信息

Chronic Obstr Pulm Dis. 2021 Jan;8(1):91-9. doi: 10.15326/jcopdf.2020.0170.

Abstract

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is characterized by recurrent exacerbations. Macrophages play a critical role in immune response and tissue repair in COPD. Airway macrophages (AM) are exposed to environmental exposures which are retained in the cytoplasmic material. Both biomass and particulate matter have been linked to higher AM black carbon. It is unknown if AM black carbon is associated with COPD morbidity and macrophage phenotype.

METHODS

Former smokers with COPD were enrolled and sputum induction was performed to obtain airway macrophages. Macrophages underwent black carbon quantification and flow cytometry phenotyping. Health information was obtained the same day as sputum induction and prospective exacerbations were assessed by monthly telephone calls.

RESULTS

We studied 30 former smokers with COPD who had a mean age of 67 years and mean forced expiratory volume in 1 second (FEV)% predicted of 60.8%. Higher AM black carbon content was associated with increased total exacerbations and severe exacerbations and reduced CD80 expression.

CONCLUSION

AM black carbon association with respiratory morbidity is largely unexplored and this is the first study to identify association with prospective exacerbations. Macrophages expressed reduced CD80, a surface marker providing costimulatory signals required for development of antigen-specific immune responses. Our findings suggest that reduced CD80 expression is the pathophysiologic mechanism for the association of AM black carbon content and increased exacerbations. Therefore, beyond solely serving as a marker for increased exposures, AM black carbon content may be a predictor of future exacerbations given a macrophage less equipped to respond to an acute infectious exposure.

摘要

背景

慢性阻塞性肺疾病(COPD)的特征是反复急性加重。巨噬细胞在COPD的免疫反应和组织修复中起关键作用。气道巨噬细胞(AM)暴露于环境暴露物中,这些暴露物保留在细胞质物质中。生物质和颗粒物都与较高的AM黑碳有关。尚不清楚AM黑碳是否与COPD发病率和巨噬细胞表型相关。

方法

招募患有COPD的既往吸烟者,进行痰液诱导以获取气道巨噬细胞。对巨噬细胞进行黑碳定量和流式细胞术表型分析。在痰液诱导当天获取健康信息,并通过每月电话随访评估前瞻性急性加重情况。

结果

我们研究了30名患有COPD的既往吸烟者,他们的平均年龄为67岁,预计第1秒用力呼气容积(FEV)%为60.8%。较高的AM黑碳含量与总急性加重次数和严重急性加重次数增加以及CD80表达降低相关。

结论

AM黑碳与呼吸系统发病率的关联在很大程度上尚未得到探索,这是第一项确定与前瞻性急性加重相关的研究。巨噬细胞表达的CD80减少,CD80是一种表面标志物,提供抗原特异性免疫反应发展所需的共刺激信号。我们的研究结果表明,CD80表达降低是AM黑碳含量与急性加重次数增加之间关联的病理生理机制。因此,AM黑碳含量可能不仅仅是暴露增加的标志物,鉴于巨噬细胞对急性感染暴露的反应能力较弱,它可能是未来急性加重的预测指标。

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