Increased activation of fibrocytes in patients with chronic obstructive asthma through an epidermal growth factor receptor-dependent pathway.
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.
Pulmonary Disease Research Center, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
Chun-Hua
CH
Wang
Chien-Da
CD
Huang
Horng-Chyuan
HC
Lin
Tzu-Ting
TT
Huang
Kang-Yun
KY
Lee
Yu-Lun
YL
Lo
Shu-Min
SM
Lin
Kian Fan
KF
Chung
Han-Pin
HP
Kuo
D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000111:Acetylcysteine / Q000494:pharmacology; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001249:Asthma / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D012129:Respiratory Function Tests; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020032:Tyrphostins / Q000494:pharmacology
D018952:Antigens, CD34; D024042:Collagen Type I; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D006861:Hydrogen Peroxide; C512478:EGFR protein, human; D066246:ErbB Receptors; D017493:Leukocyte Common Antigens; D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000077156:Gefitinib; D000111:Acetylcysteine