151. SH2-Bβ expression in alveolar macrophages in BAL fluid of asthmatic guinea pigs and its role in NGF–TrkA-mediated asthma.
- Author
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Li LI, Lingfei KONG, Xiubin FANG, Changlin JIANG, Yating WANG, Zhaoshuang ZHONG, Qiyu SUN, Guozhong GU, Dongqing ZHENG, Rui MENG, and Jian KANG
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ASTHMA , *NERVE growth factor , *PROTEIN-tyrosine kinases , *ASTHMATICS , *IMMUNOFLUORESCENCE , *GUINEA pigs - Abstract
Background and objective: Nerve growth factor (NGF)/tyrosine kinase receptor A (TrkA) signalling may play an important role in the pathogenesis of asthma, and SH2-Bβ, a TrkA-binding protein, modulates the NGF signalling pathway. In this study, SH2-Bβ expression in alveolar macrophages (AM) in guinea pig BAL fluid and its role in asthma pathogenesis through the NGF–TrkA signalling pathway were investigated. Methods: Guinea pigs were randomized into five groups: control, a model of asthma, anti-SH2-Bβ antibody treatment, anti-NGF antibody treatment and anti-TrkA antibody treatment. The asthmatic model was established in guinea pigs by inhalation of ovalbumin. Specific anti-SH2-Bβ, anti-NGF and anti-TrkA antibodies were administered and AM were isolated from BAL fluid to assess SH2-Bβ expression using an immunofluorescence assay. SH2-Bβ and TrkA protein expression were determined by western blotting, IL-1β and IL-4 levels in the BAL fluid supernatants were determined by ELISA, and pathological changes in the bronchi and lung tissues were examined by HE staining. Results: Lymphocyte, eosinophil and total inflammatory cell numbers in BAL fluid were significantly higher in the asthma model group than in the other groups ( P < 0.01). NGF expression in the asthma model group was significantly higher than that in the PBS control group ( P < 0.01). SH2-Bβ was expressed in AM of control animals and expression was significantly higher in the asthma model than in the other groups ( P < 0.01). TrkA protein expression was significantly higher in the asthma model group than in the PBS group ( P < 0.01), and treatment with anti-NGF antibody resulted in significant reduction of TrkA expression ( P < 0.01). Conclusions: SH2-Bβ is expressed in AM of normal guinea pigs, and SH2-Bβ may participate in asthma pathogenesis through the NGF–TrkA signalling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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