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

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 TH2 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.

Current and future biomarkers in allergic asthma

“…Sputum levels of uric acid, ECP, CXCL-10 and TNF-a are elevated upon asthma exacerbation (180,181). In the peripheral blood, CD45 severe asthma (182). CXCR4 and CCR7 mediated fibrocyte transmigration in acute asthma exacerbation and in chronic obstructive asthma, respectively (183).…”

Fibrocytes and Fibrovascular Membrane Formation in Proliferative Diabetic Retinopathy

“…Cultured monocytes can differentiate into fibrocytes, but it is still unclear if maturation of fibrocytes occurs in the bone marrow, the circulation, or after migration to the tissues. Fibrocytes contribute to the innate response to injury and tissue remodeling, and these cells also mediate fibrogenesis in a number of systemic and organ-specific fibrosing disorders, such as renal fibrosis, 10 ischemic cardiomyopathy, 11,12 pulmonary fibrosis, 13,14 asthma, [15][16][17][18] and keloid scarring. 19 Recently, Abu El-Asrar et al 20,21 demonstrated that circulating fibrocytes contributed to the population of myofibroblasts in the epiretinal membranes of patients with PDR and iovs.arvojournals.org j ISSN: 1552-5783 proliferative vitreoretinopathy.…”

Tumor Necrosis Factor-alpha and Transforming Growth Factor-beta Synergistically Upregulate Endothelin-1 Expression in Human Bronchial Epithelial Cells BEAS-2B

“…The exact mechanistic relationship between airway remodeling and TNF-has not been clari ed ; however, it is possible that endothelin-1, induced In turn, TGFis a multifunctional cytokine that exerts many biological effects including immunosuppressive and in ammation-regulatory effects. On the other hand, TGF-also seems to be pivotal in the pathogenesis of airway remodeling and severe asthma 17 , inducing brocyte differentiation and stimulating both fibroblast proliferation and the synthesis of extracellular matrix proteins 18 . TGFcan also initiate the epithelial-mesenchymal transition, a mechanism characterized by the acquisition of a mesenchymal phenotype in bronchial epithelial cells and observed in the epithelial cells of patients with severe asthma 19 .…”