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

Authors: Lee, SH  Kim, KH  Kim, JM  Yoon, SH  Kim, TH  Park, SW  Park, JS  Uh, ST  Lee, HS  Kim, YH 
Citation: Lee SH, etal., Am J Respir Crit Care Med. 2011 Sep 1;184(5):528-36.
Pubmed: (View Article at PubMed) PMID:21169467
DOI: Full-text: DOI:10.1164/rccm.201006-0951OC

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-b 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 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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CRRD Object Information
CRRD ID: 5509920
Created: 2011-11-11
Species: All species
Last Modified: 2011-11-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.