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在慢性阻塞性肺疾病中,气道上皮血小板活化因子受体表达明显上调。

Airway epithelial platelet-activating factor receptor expression is markedly upregulated in chronic obstructive pulmonary disease.

作者信息

Shukla Shakti Dhar, Sohal Sukhwinder Singh, Mahmood Malik Quasir, Reid David, Muller Hans Konrad, Walters Eugene Haydn

机构信息

NHMRC Centre for Research Excellence for Chronic Respiratory Disease and Lung Ageing, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.

Queensland Institute of Medical Research, Iron Metabolism Laboratory, Brisbane, Queensland, Australia.

出版信息

Int J Chron Obstruct Pulmon Dis. 2014 Aug 13;9:853-61. doi: 10.2147/COPD.S67044. eCollection 2014.

Abstract

BACKGROUND

We recently published that platelet-activating factor receptor (PAFr) is upregulated on the epithelium of the proximal airways of current smokers and also in bronchial epithelial cells exposed to cigarette smoke extract. These treated cells also showed upregulation of Streptococcus pneumoniae adhesion. Bacterial wall phosphorylcholine specifically binds to PAFr expressed on airway epithelium, thus facilitating adherence and tissue invasion, which may be relevant to chronic obstructive pulmonary disease (COPD). Moreover, the use of inhaled corticosteroids (ICS) in COPD patients is associated with an increased risk of invasive respiratory pneumococcal infections.

OBJECTIVE

In this study, we have investigated whether PAFr expression is especially upregulated in airway epithelium in COPD patients and whether this expression may be modulated by ICS therapy.

METHODS

We cross-sectionally evaluated PAFr expression in bronchial biopsies from 15 COPD patients who were current smokers (COPD-smokers) and 12 COPD-ex-smokers, and we compared these to biopsies from 16 smokers with normal lung function. We assessed immunostaining with anti-PAFr monoclonal antibody. We also used material from a previous double-blinded randomized placebo-controlled 6-month ICS intervention study in COPD patients to explore the effect of ICS on PAFr expression. We employed computer-aided image analysis to quantify the percentage of epithelium stained for PAFr.

RESULTS

Markedly enhanced expression of PAFr was found in both COPD-smokers (P<0.005) and COPD-ex-smokers (P<0.002) compared to smokers with normal lung function. There was little evidence that PAFr expression was affected by ICS therapy over 6 months.

CONCLUSION

Epithelial PAFr expression is upregulated in smokers, especially in those with COPD, and is not obviously affected by ICS therapy.

摘要

背景

我们最近发表的研究表明,血小板活化因子受体(PAFr)在当前吸烟者近端气道上皮以及暴露于香烟烟雾提取物的支气管上皮细胞中上调。这些处理过的细胞还显示出肺炎链球菌黏附的上调。细菌壁磷酰胆碱特异性结合气道上皮上表达的PAFr,从而促进黏附和组织侵袭,这可能与慢性阻塞性肺疾病(COPD)相关。此外,COPD患者使用吸入性糖皮质激素(ICS)与侵袭性呼吸道肺炎球菌感染风险增加有关。

目的

在本研究中,我们调查了COPD患者气道上皮中PAFr表达是否特别上调,以及这种表达是否可能受到ICS治疗的调节。

方法

我们对15名当前吸烟者(COPD吸烟者)和12名已戒烟的COPD患者的支气管活检组织中的PAFr表达进行了横断面评估,并将其与16名肺功能正常的吸烟者的活检组织进行比较。我们用抗PAFr单克隆抗体评估免疫染色。我们还使用了之前一项针对COPD患者的为期6个月的双盲随机安慰剂对照ICS干预研究的材料,以探讨ICS对PAFr表达的影响。我们采用计算机辅助图像分析来量化PAFr染色的上皮细胞百分比。

结果

与肺功能正常的吸烟者相比,COPD吸烟者(P<0.005)和已戒烟的COPD患者(P<0.002)中PAFr的表达均显著增强。几乎没有证据表明PAFr表达在6个月的ICS治疗后受到影响。

结论

吸烟者,尤其是COPD患者,上皮PAFr表达上调,且不受ICS治疗的明显影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cf1/4137917/9a7d00ef81fc/copd-9-853Fig1.jpg

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