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慢性阻塞性肺疾病患者肺肥大细胞群体的改变。

Alterations in lung mast cell populations in patients with chronic obstructive pulmonary disease.

机构信息

Department of Respiratory Medicine and Allergology, Lund University Hospital, Lund, Sweden.

出版信息

Am J Respir Crit Care Med. 2010 Feb 1;181(3):206-17. doi: 10.1164/rccm.200906-0932OC. Epub 2009 Nov 19.

DOI:10.1164/rccm.200906-0932OC
PMID:19926870
Abstract

RATIONALE

Mast cells have important roles in innate immunity and tissue remodeling but have remained poorly studied in inflammatory airway diseases like chronic obstructive pulmonary disease (COPD).

OBJECTIVES

To perform a detailed histological characterization of human lung mast cell populations at different severities of COPD, comparing with smoking and never-smoking control subjects.

METHODS

Mast cells were analyzed in lung tissues from patients with mild to very severe COPD, GOLD I-IV (n = 25, 10 of whom were treated with corticosteroids). Never-smokers and smokers served as controls. The density, morphology, and molecular characteristics of mucosal and connective tissue mast cells (MC(T) and MC(TC), respectively) were analyzed in several lung regions.

MEASUREMENTS AND MAIN RESULTS

In all compartments of COPD lungs, especially at severe stages, the MC(TC) population increased in density, whereas the MC(T) population decreased. The net result was a reduction in total mast cell density. This phenomenon was paralleled by increased numbers of luminal mast cells, whereas the numbers of terminal transferase dUTP nick end labeling (TUNEL)(+) apoptotic mast cells remained unchanged. In COPD lungs, the MC(T) and MC(TC) populations showed alterations in morphology and expression of CD88 (C5a-R), transforming growth factor (TGF)-beta, and renin. Statistically significant correlations were found between several COPD-related mast cell alterations and lung function parameters.

CONCLUSIONS

As COPD progresses to its severe stages, the mast cell populations in the lung undergo changes in density, distribution, and molecular expression. In COPD lungs, these novel histopathological features were found to be correlated to lung function and they may thus have clinical consequences.

摘要

背景

肥大细胞在先天免疫和组织重塑中具有重要作用,但在慢性阻塞性肺疾病(COPD)等炎症性气道疾病中的研究仍不完善。

目的

对不同严重程度 COPD 患者的人肺肥大细胞群体进行详细的组织学特征分析,并与吸烟和不吸烟对照者进行比较。

方法

分析了轻度至重度 COPD(GOLD I-IV 期)患者、10 例接受皮质类固醇治疗患者的肺组织中的肥大细胞,从不吸烟者和吸烟者作为对照。分析了几个肺区黏膜和结缔组织肥大细胞(MC(T)和 MC(TC))的密度、形态和分子特征。

测量和主要结果

在 COPD 肺的所有区域,尤其是在严重阶段,MC(TC)群体的密度增加,而 MC(T)群体减少。结果是总肥大细胞密度降低。这种现象与腔内肥大细胞数量的增加平行,而末端转移酶 dUTP 缺口末端标记(TUNEL)(+)凋亡肥大细胞的数量保持不变。在 COPD 肺中,MC(T)和 MC(TC)群体的形态和 CD88(C5a-R)、转化生长因子(TGF)-β和肾素的表达发生改变。发现几种与 COPD 相关的肥大细胞改变与肺功能参数之间存在统计学显著相关性。

结论

随着 COPD 进展到严重阶段,肺中的肥大细胞群体在密度、分布和分子表达上发生变化。在 COPD 肺中,这些新的组织病理学特征与肺功能相关,因此可能具有临床意义。

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