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Am. J. Respir. Crit. Care Med. · Sep 2011
Comparative StudyRelationship between group-specific component protein and the development of asthma.
- Tae Hoon Kim and Soo-Taek Uh.
- Genome Research Center for Allergy and Respiratory disease, Soonchunhyang University Hospital, Bucheon, Gyeonggi-do, Republic of Korea.
- Am. J. Respir. Crit. Care Med.. 2011 Sep 1;184(5):528-36.
RationaleAirway inflammation and remodeling during asthma are attributed to the altered expression of biologically relevant proteins.ObjectivesTo 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.MethodsLiquid 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 ResultsBased 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.ConclusionsGc 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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