循环纤维细胞的数量、活化及分化与哮喘严重程度相关。

Number, activation, and differentiation of circulating fibrocytes correlate with asthma severity.

作者信息

Shipe Ryan, Burdick Marie D, Strieter Brett A, Liu Ling, Shim Yun Michael, Sung Sun-sang, Teague W Gerald, Mehrad Borna, Strieter Robert M, Rose C Edward

机构信息

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.

Pulmonary Division, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.

出版信息

J Allergy Clin Immunol. 2016 Mar;137(3):750-7.e3. doi: 10.1016/j.jaci.2015.07.037. Epub 2015 Sep 12.

DOI:10.1016/j.jaci.2015.07.037

PMID:26371837

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4836439/

Abstract

BACKGROUND

A biomarker that predicts poor asthma control would be clinically useful. Fibrocytes are bone marrow-derived circulating progenitor cells that have been implicated in tissue fibrosis and T(H)2 responses in asthmatic patients.

OBJECTIVE

We sought to test the hypothesis that the concentration and activation state of peripheral blood fibrocytes correlates with asthma severity.

METHODS

By using fluorescence-activated cell sorting analysis, fibrocytes (CD45(+) and collagen 1 Col1) were enumerated and characterized in the buffy coats of fresh peripheral blood samples from 15 control subjects and 40 asthmatic patients.

RESULTS

Concentrations of peripheral blood total (CD45(+)Col1(+)), activated (the TGF-β transducing protein phosphorylated SMAD2/3 p-SMAD2/3 or phosphorylated AKT p-AKT), and differentiated (α-smooth muscle actin α-SMA) fibrocytes were increased in asthmatic patients compared with control subjects. The increase in total and CD45(+)Col1(+)CXCR4(+) fibrocytes was primarily seen in patients with severe asthma (Global Initiative for Asthma steps 4-5) as opposed to those with milder asthma (Global Initiative for Asthma steps 1-3). In addition, numbers of circulating α-SMA(+) and α-SMA(+)CXCR4(+) fibrocytes were increased in asthmatic patients experiencing an asthma exacerbation in the preceding 12 months. A significant correlation (P < .05) was observed between CD45(+)Col1(+)CXCR4(+) fibrocytes and the activation phenotypes CD45(+)Col1(+)p-SMAD2/3(+) and CD45(+)Col1(+)p-AKT(+).

CONCLUSION

There was correlation between circulating fibrocyte subsets and asthma severity, and there was an increased number of activated/differentiated fibrocytes in circulating blood of asthmatic patients experiencing an exacerbation in the preceding 12 months.

摘要

背景

一种能够预测哮喘控制不佳的生物标志物在临床上将具有重要意义。纤维细胞是源自骨髓的循环祖细胞，与哮喘患者的组织纤维化和T(H)2反应有关。

目的

我们试图验证外周血纤维细胞的浓度和激活状态与哮喘严重程度相关这一假设。

方法

通过荧光激活细胞分选分析，对15名对照受试者和40名哮喘患者新鲜外周血样本的血沉棕黄层中的纤维细胞（CD45(+)和胶原蛋白1Col1）进行计数和特征分析。

结果

与对照受试者相比，哮喘患者外周血中总纤维细胞（CD45(+)Col1(+)）、激活的纤维细胞（转化生长因子-β转导蛋白磷酸化SMAD2/3p-SMAD2/3或磷酸化AKTp-AKT）和分化的纤维细胞（α-平滑肌肌动蛋白α-SMA）的浓度增加。总纤维细胞和CD45(+)Col1(+)CXCR4(+)纤维细胞的增加主要见于重度哮喘患者（全球哮喘防治创议第4 - 5级），而非轻度哮喘患者（全球哮喘防治创议第1 - 3级）。此外，在过去12个月内经历过哮喘发作的哮喘患者中，循环中的α-SMA(+)和α-SMA(+)CXCR4(+)纤维细胞数量增加。在CD45(+)Col1(+)CXCR4(+)纤维细胞与激活表型CD45(+)Col1(+)p-SMAD2/3(+)和CD45(+)Col1(+)p-AKT(+)之间观察到显著相关性（P < .05）。