Increased activation of fibrocytes in patients with chronic obstructive asthma through an epidermal growth factor receptor–dependent pathway

• Published in: Journal of allergy and clinical immunology Vol. 129; no. 5; pp. 1367 - 1376
• Main Authors: Wang, Chun-Hua, Huang, Chien-Da, Lin, Horng-Chyuan, Huang, Tzu-Ting, Lee, Kang-Yun, Lo, Yu-Lun, Lin, Shu-Min, Chung, Kian Fan, Kuo, Han-Pin
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.05.2012; Elsevier; Elsevier Limited
• Subjects: a disintegrin and metalloprotease domain 17; Acetylcysteine; Acetylcysteine - pharmacology; ADAM Proteins - metabolism; ADAM17 Protein; Adult; Allergy and Immunology; Antigens, CD34 - metabolism; Asthma; Asthma - complications; Asthma - drug therapy; Asthma - metabolism; Asthma - pathology; Biological and medical sciences; Blood Cells - drug effects; Blood Cells - metabolism; Blood Cells - pathology; CD34 antigen; CD45 antigen; Cell culture; Cell Proliferation - drug effects; Cell Transformation, Neoplastic - drug effects; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; Collagen; Collagen (type I); Collagen Type I - metabolism; Differentiation; Epidermal growth factor; epidermal growth factor receptor; Epidermal growth factor receptors; ErbB Receptors - metabolism; Female; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrocytes; Flow cytometry; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gefitinib; Humans; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Immunopathology; Kinases; Leukocyte Common Antigens - metabolism; Leukocytes (mononuclear); Ligands; Lung; lung function; Male; Medical sciences; Metalloproteinase; metalloproteinases; Middle Aged; Oxidative Stress; patients; Phosphorylation; Pneumology; Protein-tyrosine kinase; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - pathology; Quinazolines - pharmacology; Quinazolines - therapeutic use; Respiratory Function Tests; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Signal Transduction; Smooth muscle; Stem cells; Stem Cells - drug effects; Stem Cells - metabolism; Stem Cells - pathology; Transformation; tyrosine; Tyrphostins - pharmacology; Fibrocytes; EGF; HB-EGF; NPF; epidermal growth factor receptor; asthma; siRNA; H2O2; EGFR; IMDM; ADAM; α-SMA; NAC; FITC; COA; PE; TAPI-1; PerCp; NANT; oxidative stress; a disintegrin and metalloprotease domain 17; Fluorescein isothiocyanate; Hydrogen peroxide; Small interfering RNA; N-acetylcysteine; Chronic obstructive asthma; Epidermal growth factor; A disintegrin and metalloprotease domain; α-Smooth muscle actin; H 2O 2; Nonadherent non-T; Heparin-binding EGF-like growth factor; Phycoerythrin; Iscove modified Dulbecco medium; TNF protease inhibitor 1; Normal pulmonary function; Peridinin chlorophyll-protein complex; Human; Lung disease; Immunopathology; Oxidative stress; Disintegrin; Respiratory disease; Activation; Obstruction; Epidermal growth factor receptor; Asthma; Chronic; Growth factor receptor; Immunology; Bronchus disease; Obstructive pulmonary disease
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.01.038

Fibrocytes are circulating progenitor cells that are increased in asthmatic patients with chronic obstructive asthma (COA) and rapid decrease in lung function. Fibrocytes from patients with COA have a greater capacity for proliferation and differentiation. We investigated whether epidermal growth factor receptor (EGFR) activation mediated the proliferation of fibrocytes in patients with COA and whether oxidative stress was involved in this activation. Circulating fibrocytes from nonadherent non–T-cell mononuclear cell fractions from healthy subjects, asthmatic patients with normal pulmonary function, and patients with COA were determined by using flow cytometric coexpression of collagen I, CD45, and CD34 or EGFR or a disintegrin and metalloprotease domain 17 and placed in culture. Expression of EGFR was increased in fibrocytes from patients with COA compared with that seen in patients with NPF. AG1478 and gefitinib, inhibitors of EGFR tyrosine kinase, reduced fibrocyte proliferation and myofibroblast transformation. Increased expression of EGFR and fibrocyte proliferation and transformation were induced by hydrogen peroxide, and these effects were inhibited by N-acetylcysteine. Enhanced fibrocyte proliferation and transformation found in patients with COA might be mediated through an oxidant-sensitive EGFR-dependent pathway.