Fibrocyte localization to the airway smooth muscle is a feature of asthma.
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.
Saunders
Ruth
R
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
Siddiqui
Salman
S
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
Kaur
Davinder
D
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
Doe
Camille
C
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
Sutcliffe
Amanda
A
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
Hollins
Fay
F
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
Bradding
Peter
P
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
Wardlaw
Andrew
A
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
Brightling
Christopher E
CE
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester.
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
D010982:Platelet-Derived Growth Factor; D019707:Receptors, Chemokine