Relationship between group-specific component protein and the development of asthma.
Am J Respir Crit Care Med
; 184(5): 528-36, 2011 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-21169467
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 MAINRESULTS:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Líquido da Lavagem Broncoalveolar
/
Proteínas
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
Limite:
Adult
/
Animals
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article