title: Fibrocyte localization to the airway smooth muscle is a feature of asthma.
abstract: BACKGROUND
  Airway smooth muscle (ASM) hyperplasia is a hallmark of asthma that is associated with disease severity and persistent airflow obstruction.
  
  
  OBJECTIVE
  We sought to investigate whether fibrocytes, a population of peripheral blood mesenchymal progenitors, are recruited to the ASM compartment in asthma.
  
  
  METHODS
  We assessed the number of fibrocytes in bronchial biopsy specimens and peripheral blood from subjects with mild-to-severe refractory asthma versus healthy control subjects. In vitro we investigated potential mechanisms controlling fibrocyte migration toward the ASM bundle.
  
  
  RESULTS
  Fifty-one subjects with asthma and 33 control subjects were studied. In bronchial biopsy specimens, the number of fibrocytes was increased in the lamina propria of subjects with severe refractory asthma (median [interquartile range] number, 1.9/mm(2) [1.7/mm(2)]) versus healthy control subjects (median [interquartile range] number, 0/mm(2) [0.3/mm(2)], P < .0001) and in the ASM bundle of subjects with asthma of all severities (subjects with severe asthma, median [interquartile range] number, 3.8/mm(2) [9.4/mm(2)]; subjects with mild-to-moderate asthma, median [interquartile range] number, 1.1/mm(2) [2.4/mm(2)]); healthy control subjects, (median [interquartile range] number, 0/mm(2) [0/mm(2)]); P = .0004). In the peripheral blood the fibrocyte number was also increased in subjects with severe refractory asthma (median [interquartile range] number, 1.4 x 10(4)/mL [2.6 x 10(4)/mL]) versus healthy control subjects (median [interquartile range] number, 0.4 x 10(4)/mL [1.0 x 10(4)/mL], P = .002). We identified that in vitro ASM promotes fibrocyte chemotaxis and chemokinesis (distance of migration after 4.5 hours, 31 microm [2.9 microm] vs 17 microm [2.4 microm], P = .0001), which was in part mediated by platelet-derived growth factor (mean inhibition by neutralizing antibody, 16% [95% CI, 2% to 32%], P = .03) but not by activation of chemokine receptors.
  
  
  CONCLUSIONS
  This study provides the first evidence that fibrocytes are present in the ASM compartment in asthma and that ASM can augment fibrocyte migration. The importance of fibrocytes in the development of ASM hyperplasia and airway dysfunction in asthma remains to be determined.
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
authors.forename: Ruth
authors.initials: R
authors.lastname: Saunders
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
authors.forename: Salman
authors.initials: S
authors.lastname: Siddiqui
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
authors.forename: Davinder
authors.initials: D
authors.lastname: Kaur
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
authors.forename: Camille
authors.initials: C
authors.lastname: Doe
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
authors.forename: Amanda
authors.initials: A
authors.lastname: Sutcliffe
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
authors.forename: Fay
authors.initials: F
authors.lastname: Hollins
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
authors.forename: Peter
authors.initials: P
authors.lastname: Bradding
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wardlaw
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
mesh_terms: D000328:Adult; D001249:Asthma / Q000473:pathology*; D002465:Cell Movement; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009130:Muscle, Smooth / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000473:pathology*; D019707:Receptors, Chemokine / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D019707:Receptors, Chemokine