Relationship between Group-Specific Component Protein and the Development of Asthma
- Authors
- Lee, Shin-Hwa; Kim, Kyung-Hun; Kim, Jin-Moo; Yoon, Sang-Hyuk; Kim, Tae Hoon; Park, Sung-Woo; Park, Jong-Sook; Uh, Soo-Taek; Lee, Ho Sung; Kim, Yong Hoon; Kang, Jin Hyun; Chung, Il Yup; Paik, Young Ki; Rhim, Taiyoun; Park, Choon-Sik
- Issue Date
- 1-Sep-2011
- Publisher
- American Thoracic Society
- Keywords
- asthma; BAL; Gc; proteomics; 2D electrophoresis; therapeutics
- Citation
- American Journal of Respiratory and Critical Care Medicine, v.184, no.5, pp 528 - 536
- Pages
- 9
- Journal Title
- American Journal of Respiratory and Critical Care Medicine
- Volume
- 184
- Number
- 5
- Start Page
- 528
- End Page
- 536
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/16211
- DOI
- 10.1164/rccm.201006-0951OC
- ISSN
- 1073-449X
1535-4970
- Abstract
- Rationale: Airway inflammation and remodeling during asthma are attributed to the altered expression of biologically relevant proteins. Objectives: To search for asthma-specific proteins in bronchoalveolar lavage fluid (BAL) from individuals with asthma and to validate the identified proteins in an experimental model of asthma. Methods: Liquid chromatography-tandem mass spectrometry was performed to identify proteins in BAL fluid found by two-dimensional electrophoresis (2DE) to be differentially expressed in subjects with asthma versus control subjects. Group-specific component (Gc) and mRNA levels were measured using an ELISA, Western blots, and PCR. A neutralization study using an antibody against Gc protein was performed in an experimental asthma model. Measurements and Main Results: Based on 2DE, 15 proteins were significantly up-regulated or down-regulated in eight subjects with asthma compared with eight control subjects. The protein levels of Gc, hemopexin, and haptoglobin-beta were increased, whereas the alpha(1)-antitrypsin and glutathione S-transferase levels were decreased in subjects with asthma. The Gc concentration in BAL fluid was significantly elevated in 67 subjects with asthma compared with that in 22 control subjects (P < 0.009). The Gc was significantly correlated with the neutrophil percentage in BAL fluid of subjects with asthma (P = 0.001). Gc mRNA and protein levels were higher in ovalbumin-sensitized/challenged asthma mice than in sham-treated mice. Gc protein were expressed on alveolar macrophages and on epithelial cells. Treatment with an anti-Gc antibody dose-dependently reduced the ovalbumin sensitization/challenge-induced enhancement of airway hyperreactivity, airway inflammation, goblet cell hyperplasia, and levels of eotaxin, interleukin-4, -5, and -13, and interferon-g. Conclusions: Gc may be involved in the development of asthma, and the neutralization of Gc protein could be a therapeutic strategy for asthma.
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Collections - College of Medicine > Department of Internal Medicine > 1. Journal Articles
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