Increased activation of fibrocytes in patients with chronic obstructive asthma through an epidermal growth factor receptor–dependent pathway - 28/04/12
Corresponding author: Han-Pin Kuo, MD, PhD, Pulmonary Disease Research Center, Department of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa North Rd, Taipei, Taiwan.Abstract |
Background |
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.
Objective |
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.
Methods |
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.
Results |
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.
Conclusions |
Enhanced fibrocyte proliferation and transformation found in patients with COA might be mediated through an oxidant-sensitive EGFR-dependent pathway.
Le texte complet de cet article est disponible en PDF.Key words : Fibrocytes, epidermal growth factor receptor, a disintegrin and metalloprotease domain 17, asthma, oxidative stress
Abbreviations used : ADAM, ⍺-SMA, COA, EGF, EGFR, FITC, HB-EGF, H2O2, IMDM, NAC, NANT, NPF, PE, PerCp, siRNA, TAPI-1
Plan
| Supported by Taiwan National Science Council grant NSC-96-2628-B-182-22-my3, a Chang Gung Research Project grant (CMRPG 371091), and a UK Wellcome Trust grant (no. 085935). |
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| Disclosure of potential conflict of interest: C.-H. Wang receives research support from the National Science Council, Taiwan. K. F. Chung has consultant arrangements with Gilead, is on advisory boards for Merck and GlaxoSmithKline, and receives research support from MRC UK, Asthma UK, and the Wellcome Trust. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 5
P. 1367-1376 - mai 2012 Retour au numéro
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