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Increased activation of fibrocytes in patients with chronic obstructive asthma through an epidermal growth factor receptor–dependent pathway
Ist Teil von
Journal of allergy and clinical immunology, 2012-05, Vol.129 (5), p.1367-1376
Ort / Verlag
New York, NY: Mosby, Inc
Erscheinungsjahr
2012
Quelle
MEDLINE
Beschreibungen/Notizen
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.