Fibrocyte localization to the airway smooth muscle is a feature of asthma

• Published in: Journal of allergy and clinical immunology Vol. 123; no. 2; pp. 376 - 384
• Main Authors: Saunders, Ruth, Siddiqui, Salman, Kaur, Davinder, Doe, Camille, Sutcliffe, Amanda, Hollins, Fay, Bradding, Peter, Wardlaw, Andrew, Brightling, Christopher E.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2009; Elsevier; Elsevier Limited
• Subjects: Adult; airway smooth muscle; Allergy and Immunology; Asthma; Asthma - pathology; Biological and medical sciences; Cell Movement; Chronic illnesses; Collagen; Disease; Drug therapy; Female; Flow cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Male; mast cells; Medical sciences; Mesenchymal Stem Cells - pathology; Middle Aged; Mortality; Mucous Membrane - pathology; Muscle, Smooth - pathology; Platelet-Derived Growth Factor - metabolism; Pulmonary Fibrosis - pathology; Receptors, Chemokine - metabolism; remodeling; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Smooth muscle; α-SMA; remodeling; FITC; GINA; PDGF; RPE; airway smooth muscle; ASM; mast cells; Asthma; Fluorescein isothiocyanate; Platelet-derived growth factor; α-Smooth muscle actin; R-phycoerythrin; Global Initiative for Asthma; Lung disease; Immunopathology; Respiratory disease; Smooth muscle; Remodeling; Respiratory system; Respiratory tract; Immunology; Bronchus disease; Mast cell; Obstructive pulmonary disease; Localization
• DOI: 10.1016/j.jaci.2008.10.048
• ISSN: 0091-6749

Airway smooth muscle (ASM) hyperplasia is a hallmark of asthma that is associated with disease severity and persistent airflow obstruction. We sought to investigate whether fibrocytes, a population of peripheral blood mesenchymal progenitors, are recruited to the ASM compartment in asthma. 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. 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 × 10 4/mL [2.6 × 10 4/mL]) versus healthy control subjects (median [interquartile range] number, 0.4 × 10 4/mL [1.0 × 10 4/mL], P = .002). We identified that in vitro ASM promotes fibrocyte chemotaxis and chemokinesis (distance of migration after 4.5 hours, 31 μm [2.9 μm] vs 17 μm [2.4 μm], 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. 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.