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

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• 作者：Chun-Hua Wang ; MD^a ; ^b ; Chien-Da Huang ; MD^a ; Horng-Chyuan Lin ; MD^a ; ^b ; Tzu-Ting Huang ; BS^a ; Kang-Yun Lee ; MD ; PhD^a ; Yu-Lun Lo ; MD^a ; Shu-Min Lin ; MD^a ; Kian Fan Chung ; MD ; DSc^d ; Han-Pin Kuo ; MD ; PhD^a ; ^c ; ^{q8828@ms11.hinet.net}
• 关键词：Fibrocytes ; epidermal growth factor receptor ; a disintegrin and metalloprotease domain 17 ; asthma ; oxidative stress
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 期刊代码：158_00916749
• 类别：med
• 出版时间：May, 2012
• 卷：129
• 期：5
• 页码：1367-1376
• 文件大小：1182 K

摘要

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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聽through an oxidant-sensitive EGFR-dependent pathway.