Airway fibroblasts exhibit a synthetic phenotype in severe asthma

• Published in: Journal of allergy and clinical immunology Vol. 115; no. 3; pp. 534 - 540
• Main Authors: Lewis, Christina C., Chu, Hong Wei, Westcott, Jay Y., Tucker, Alan, Langmack, Esther L., Sutherland, E. Rand, Kraft, Monica
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.03.2005; Elsevier Limited
• Subjects: Adult; airway fibroblasts; Airway management; Asthma; Asthma - genetics; Asthma - immunology; Cells, Cultured; Collagen; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts - drug effects; Fibroblasts - immunology; Fibroblasts - metabolism; Genotype & phenotype; Humans; Lung - immunology; Lung - metabolism; Male; PDGF; Phenotype; Pilot Projects; Platelet-Derived Growth Factor - immunology; Platelet-Derived Growth Factor - pharmacology; Procollagen - biosynthesis; Proto-Oncogene Proteins c-sis; Receptors, Platelet-Derived Growth Factor - immunology; Receptors, Platelet-Derived Growth Factor - metabolism; Rodents; Smooth muscle; DMEM; FVC; PDGF; PDGFR; asthma; IGF-1; airway fibroblasts
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2004.11.051

Platelet-derived growth factor (PDGF) may have a significant role in airway remodeling in asthma, because it is a powerful inductor of many airway fibroblast activities such as collagen synthesis. To determine whether PDGF is a significant contributor to airway remodeling in patients with asthma by enhancing airway fibroblast procollagen I expression. Six normal controls without asthma, 10 subjects with mild to moderate asthma, and 5 subjects with severe asthma underwent bronchoscopy with endobronchial biopsy. Biopsies were placed in Dulbecco modified Eagle medium and fibroblasts cultured in the presence and absence of PDGF isoforms -AA, -BB, and -AB (1, 5, 10, 100 ng/mL) and insulin-like growth factor 1 (100 ng/mL). Fibroblast procollagen I and PDGF receptors (PDGFRs) α and β expression were determined by ELISA. Platelet-derived growth factor BB significantly enhanced fibroblast procollagen I expression in patients with severe asthma compared with patients with mild/moderate asthma and normal controls. Furthermore, the baseline fibroblast expression of PDGFR-β was significantly greater in patients with severe asthma compared with the other groups. This pilot study suggests that airway fibroblasts from patients with severe asthma exhibit a synthetic phenotype, which may be driven by the overexpression of PDGFR-β.