title: 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 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(+).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
authors.forename: Ryan
authors.initials: R
authors.lastname: Shipe
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
authors.forename: Marie D
authors.initials: MD
authors.lastname: Burdick
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Strieter
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
authors.forename: Yun Michael
authors.initials: YM
authors.lastname: Shim
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
authors.forename: Sun-sang
authors.initials: SS
authors.lastname: Sung
authors.affiliation: Pulmonary Division, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
authors.forename: Borna
authors.initials: B
authors.lastname: Mehrad
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strieter
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va. Electronic address: cer@virginia.edu.
authors.forename: C Edward
authors.initials: CE
authors.lastname: Rose
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D001249:Asthma / Q000097:blood* / Q000175:diagnosis*; D015415:Biomarkers; D016022:Case-Control Studies; D002452:Cell Count; D002454:Cell Differentiation; D002648:Child; D003239:Connective Tissue Cells / Q000166:cytology* / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers
keywords: Asthma; asthma severity; biomarker; fibrocytes; peripheral blood