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-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: Shin-Hwa Lee, Kyung-Hun Kim, Jin-Moo Kim, Sang-Hyuk Yoon, Tae Hoon Kim, Sung-Woo Park, Jong-Sook Park, Soo-Taek Uh, Ho Sung Lee, Yong Hoon Kim
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 184 Issue 5 Pg. 528-36 (Sep 01 2011) ISSN: 1535-4970 [Electronic] United States
• PMID: 21169467 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proteins
• RNA, Messenger
• Interleukin-4
• Glutathione Transferase

Topics

• Adult
• Animals
• Asthma (etiology, metabolism, physiopathology)
• Blotting, Western
• Bronchoalveolar Lavage Fluid (chemistry)
• Chromatography, Liquid
• Enzyme-Linked Immunosorbent Assay
• Female
• Follow-Up Studies
• Glutathione Transferase (genetics, metabolism)
• Humans
• Interleukin-4 (genetics, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Middle Aged
• Polymerase Chain Reaction
• Proteins (genetics, metabolism)
• RNA, Messenger (analysis)
• Tandem Mass Spectrometry