title: Relationship between group-specific component protein and the development of asthma.
abstract: BACKGROUND
  Airway inflammation and remodeling during asthma are attributed to the altered expression of biologically relevant proteins.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Genome Research Center for Allergy and Respiratory disease, Soonchunhyang University Hospital, Bucheon, Gyeonggi-do, Republic of Korea.
authors.forename: Shin-Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Kim
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Kim
authors.forename: Sang-Hyuk
authors.initials: SH
authors.lastname: Yoon
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Jong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Lee
authors.forename: Yong Hoon
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002853:Chromatography, Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D053719:Tandem Mass Spectrometry
chemical_list: D011506:Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D005982:Glutathione Transferase