Relationship between Group-Specific Component Protein and the Development of Asthma

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.