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

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• 作者：Ryan Shipe ; MD^a ; Marie D. Burdick ; BS^a ; Brett A. Strieter^a ; Ling Liu ; BS^a ; Yun Michael Shim ; MD^a ; Sun-sang Sung ; PhD^a ; W. Gerald Teague ; MD^b ; Borna Mehrad ; MBBS^a ; Robert M. Strieter ; MD^a ; ^&lowast ; ; C. Edward Rose Jr. ; MD^a ; ^{cer@virginia.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Asthma ; asthma severity ; fibrocytes ; peripheral blood ; biomarker
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：137
• 期：3
• 页码：750-757.e3
• 全文大小：1218 K

文摘

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_H2 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.