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

作者：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, Jr.^*

来源：Journal of Allergy and Clinical Immunology, 2016, 137(3): 750-+.

DOI：10.1016/j.jaci.2015.07.037

• Asthma
• asthma severity
• fibrocytes
• peripheral blood
• biomarker

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(+) [Col1](+)) were enumerated and characterized in the buffy coats of fresh peripheral blood samples from+5 control subjects and 40 asthmatic patients.
Results: Concentrations of peripheral blood total (CD45(+)Col1(+)), activated (the TGF-beta transducing protein phosphorylated SMAD2/3 [p-SMAD2/3](+) or phosphorylated AKT [p-AKT]1), and differentiated (alpha-smooth muscle actin [alpha-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 alpha-SMA(+) and alpha-SMA(+)CXCR4(+) fibrocytes were increased in asthmatic patients experiencing an asthma exacerbation in the preceding 12 months. Asignificant 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+2 months.

• 出版日期2016-3