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Increased Expression of Platelet-Derived Growth Factor Receptor-β in Airway Fibroblasts of Severe Asthmatics* FREE TO VIEW

Christina C. Lewis; Hong Wei Chu; Jay Y. Westcott; E. Rand Sutherland, MD, FCCP; Allen D. Stevens; Terri L. Metze; Monica Kraft, MD, FCCP
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*From the National Jewish Medical and Research Center, Denver, CO.

Correspondence to: Monica Kraft, MD, FCCP, National Jewish Medical and Research Center, 1400 Jackson St, B-120, Denver, CO 80206; e-mail: kraftm@njc.org

Chest. 2003;123(3_suppl):428S-429S. doi:10.1378/chest.123.3_suppl.428S
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Platelet-derived growth factors (PDGFs) mediate tissue repair and wound healing. PDGFs are synthesized and secreted by most inflammatory cell types present within the milieu of the asthmatic airway. We have previously reported that airway fibroblasts from severe asthmatics produce more type I procollagen in response to PDGF stimulation as compared to patients with mild asthma and normal control subjects; therefore, we hypothesized that the enhanced responsiveness to PDGFs in patients with severe asthma is linked to an increased expression of PDGF receptors. In an ongoing study, 5 subjects with severe asthma, 10 subjects with mild-to-moderate asthma, and 6 normal control subjects underwent bronchoscopy with endobronchial biopsy. Biopsies were placed in Dulbecco's modified Eagle's serum supplemented with fetal bovine serum (10%), streptomycin (100 μg/mL), penicillin (10,000 U/mL), and gentamicin (100 μg/mL), and cultured until fibroblast growth was established at > 50% confluency (approximately 8 to 20 days). Immunostaining with vimentin (Dako; Carpenteria, CA), Ab-1 (Calbiochem; San Diego, CA) and α-smooth muscle actin (Dako) confirmed fibroblast identity. To determine baseline fibroblast expression of PDGF receptors (PDGFRs) [PDGFR-α and PDGFR-β], we developed a sandwich enzyme-linked immunosorbent assay for these receptors that quantifies receptor protein levels in fibroblast cell lysates. Receptor protein levels were expressed in nanograms per 100 μg of total cell protein. There were no significant differences in baseline expression of PDGFR-α between the groups (severe, 7.6 ng/100 μg protein; mild to moderate, 12.50 ng/100 μg protein; normal control, 11.33 ng/100 μg protein; p = 0.35). However, there was a significantly greater baseline expression of PDGFR-β in the severe asthmatic group, as compared to both the mild/moderate asthmatic and normal control groups (severe, 15.20 ng/100 μg protein; mild-to-moderate, 13.30 ng/100 μg protein; normal control, 3.67 ng/100 μg protein; p = 0.0024). Our data suggests that airway fibroblasts from severe asthmatics may be of a synthetic phenotype, with altered capabilities in collagen production, as compared to those from patients with mild-to-moderate asthma and normal control subjects, and this may be driven by an increased expression of PDGFR-β.

Abbreviations: PDGF = platelet-derived growth factor; PDGFR = platelet-derived growth factor receptor

Project funded by National Heart, Lung, and Blood Institute grant 1 R01 UL64619.




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