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

Chun Hua Wang, Chien Da Huang, Horng Chyuan Lin, Tzu Ting Huang, Kang Yun Lee, Yu Lun Lo, Shu Min Lin, Kian Fan Chung, Han Pin Kuo

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1367-1376
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume129
Issue number5
DOIs
Publication statusPublished - May 2012
Externally publishedYes

Fingerprint

Epidermal Growth Factor Receptor
Asthma
Disintegrins
Lung
Myofibroblasts
Acetylcysteine
Metalloproteases
Oxidants
Protein-Tyrosine Kinases
Hydrogen Peroxide
Healthy Volunteers
Oxidative Stress
Collagen
Stem Cells

Keywords

  • a disintegrin and metalloprotease domain 17
  • asthma
  • epidermal growth factor receptor
  • Fibrocytes
  • oxidative stress

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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

In: Journal of Allergy and Clinical Immunology, Vol. 129, No. 5, 05.2012, p. 1367-1376.

Research output: Contribution to journalArticle

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. / Increased activation of fibrocytes in patients with chronic obstructive asthma through an epidermal growth factor receptor-dependent pathway. In: Journal of Allergy and Clinical Immunology. 2012 ; Vol. 129, No. 5. pp. 1367-1376.
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