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髓源性抑制细胞样成纤维细胞在慢性阻塞性肺疾病中增加,并与肺功能保留有关。

Myeloid-derived suppressor cell-like fibrocytes are increased and associated with preserved lung function in chronic obstructive pulmonary disease.

机构信息

NIHR Leicester Respiratory Biomedical Unit, Institute of Lung Health, University Hospitals of Leicester NHS Trust, Leicester, UK.

Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.

出版信息

Allergy. 2017 Apr;72(4):645-655. doi: 10.1111/all.13061. Epub 2016 Nov 10.

Abstract

BACKGROUND

The role of fibrocytes in chronic obstructive pulmonary disease (COPD) is unknown. We sought to enumerate blood and tissue fibrocytes in COPD and determine the association of blood fibrocytes with clinical features of disease.

METHODS

Utilizing flow cytometry to identify circulating, collagen type 1 cells, we found two populations: (i) CD45 CD34 (fibrocytes) and (ii) CD45 CD34 [myeloid-derived suppressor cell (MDSC)-like fibrocytes] cells in stable COPD (n = 41) and control (n = 29) subjects. Lung resection material from a separate group of subjects with (n = 11) or without (n = 11) COPD was collected for tissue fibrocyte detection. We examined circulating fibrocyte populations for correlations with clinical parameters including quantitative computed tomography (qCT) and determined pathways of association between correlated variables using a path analysis model.

RESULTS

Blood and tissue fibrocytes were not increased compared to control subjects nor were blood fibrocytes associated with lung function or qCT, but were increased in eosinophilic COPD. Myeloid-derived suppressor cell-like fibrocytes were increased in COPD compared to controls [2.3 (1.1-4.9), P = 0.038]. Our path analysis model showed that collagen type 1 intensity for MDSC-like fibrocytes was positively associated with lung function through associations with air trapping, predominately in the upper lobes.

CONCLUSION

We have demonstrated that two circulating populations of fibrocyte exist in COPD, with distinct clinical associations, but are not prevalent in proximal or small airway tissue. Blood MDSC-like fibrocytes, however, are increased and associated with preserved lung function through a small airway-dependent mechanism in COPD.

摘要

背景

成纤维细胞在慢性阻塞性肺疾病(COPD)中的作用尚不清楚。我们试图在 COPD 患者中计数血液和组织中的成纤维细胞,并确定血液成纤维细胞与疾病的临床特征之间的关联。

方法

利用流式细胞术鉴定循环中Ⅰ型胶原细胞,我们发现了两种细胞群:(i)CD45 CD34(成纤维细胞)和(ii)CD45 CD34[髓系来源抑制细胞(MDSC)样成纤维细胞],存在于稳定期 COPD(n=41)和对照组(n=29)患者中。从另一组患有(n=11)或不患有(n=11)COPD 的患者中采集肺切除组织,用于检测组织成纤维细胞。我们检查了循环成纤维细胞群与临床参数(包括定量计算机断层扫描[qCT])之间的相关性,并使用路径分析模型确定相关变量之间的关联途径。

结果

与对照组相比,血液和成纤维细胞均未增加,血液成纤维细胞也与肺功能或 qCT 无关,但在嗜酸性粒细胞性 COPD 中增加。与对照组相比,MDSC 样成纤维细胞在 COPD 中增加[2.3(1.1-4.9),P=0.038]。我们的路径分析模型表明,MDSC 样成纤维细胞的Ⅰ型胶原强度与空气潴留呈正相关,而空气潴留主要发生在上肺,通过与空气潴留的关联与肺功能相关。

结论

我们已经证明在 COPD 患者中存在两种循环成纤维细胞群,它们具有不同的临床关联,但在近端或小气道组织中并不普遍存在。然而,血液 MDSC 样成纤维细胞在 COPD 中增加,并通过小气道依赖机制与保留的肺功能相关。

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