Relationship between group-specific component protein and the development of asthma

Shin Hwa Lee, Kyung Hun Kim, Jin Moo Kim, Sang Hyuk Yoon, Tae Hoon Kim, Sung Woo Park, Jong Sook Park, Soo Taek Uh, Ho Sung Lee, Yong Hoon Kim, Jin Hyun Kang, Il Yup Chung, Young Ki Paik, Taiyoun Rhim, Choon Sik Park

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14 Citations (Scopus)

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 twodimensional 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-β were increased, whereas the a1- 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 ovalbuminsensitized/ challenged asthma mice than in sham-treated mice. Gc protein were expressed on alveolarmacrophages and on epithelial cells. Treatment with an anti-Gc antibody dose-dependently reduced the ovalbumin sensitization/challenge-induced enhancement of airway hyperreactivity, airway inflammation,gobletcellhyperplasia,and levels of eotaxin, interleukin-4, -5, and -13, and interferon-γ. Conclusions: Gcmay beinvolved in thedevelopment of asthma, andthe neutralization of Gc protein could be a therapeutic strategy for asthma.

Original languageEnglish
Pages (from-to)528-536
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume184
Issue number5
DOIs
Publication statusPublished - 2011 Sep 1

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Lee, S. H., Kim, K. H., Kim, J. M., Yoon, S. H., Kim, T. H., Park, S. W., Park, J. S., Uh, S. T., Lee, H. S., Kim, Y. H., Kang, J. H., Chung, I. Y., Paik, Y. K., Rhim, T., & Park, C. S. (2011). Relationship between group-specific component protein and the development of asthma. American Journal of Respiratory and Critical Care Medicine, 184(5), 528-536. https://doi.org/10.1164/rccm.201006-0951OC