Number, activation, and differentiation of circulating fibrocytes correlate with asthma severity.
Number, activation, and differentiation of circulating fibrocytes correlate with asthma severity.
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DOI：
10.1016/j.jaci.2015.07.037
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Rose CE Jr
中科院分区：
文献类型：
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作者：
Shipe R;Burdick MD;Strieter BA;Liu L;Shim YM;Sung SS;Teague WG;Mehrad B;Strieter RM;Rose CE Jr
预测哮喘控制不良的生物标志物将在临床上有用。纤维细胞是骨髓来源的循环祖细胞，其与哮喘患者的组织纤维化和TH 2反应有关。我们试图检验外周血纤维细胞的浓度和活化状态与哮喘严重程度相关的假设。通过使用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（CD 45+和胶原蛋白1 [Col 1]+）进行计数和表征。与对照组相比，哮喘患者外周血总（CD 45 + Col 1+）、活化（TGF-β转导蛋白磷酸化SMAD 2/3 [p-SMAD 2/3]+或磷酸化AKT [p-AKT]+）和分化（α-平滑肌肌动蛋白[α-SMA]+）纤维细胞的浓度升高。总纤维细胞和CD 4 - 5 + Col 1 + CXCR 4+纤维细胞的增加主要见于重度哮喘患者（全球哮喘倡议步骤4-5），而不是轻度哮喘患者（全球哮喘倡议步骤1-3）。此外，在前12个月内经历哮喘急性发作的哮喘患者中，循环α-SMA+和α-SMA+ CXCR 4+纤维细胞的数量增加。CD 45 + Col 1 + CXCR 4+纤维细胞与活化表型CD 45 + Col 1 + p-SMAD 2/3+和CD 45 + Col 1 +p-AKT+之间存在显著相关性（P <0.05）。循环纤维细胞亚群与哮喘严重程度之间存在相关性，在前12个月内经历急性发作的哮喘患者的循环血液中活化/分化的纤维细胞数量增加。
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 TH2 responses in asthmatic patients. We sought to test the hypothesis that the concentration and activation state of peripheral blood fibrocytes correlates with asthma severity. 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. 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+. 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.