SH2-Bβ expression in alveolar macrophages in BAL fluid of asthmatic guinea pigs and its role in NGF–TrkA-mediated asthma


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Abstract

Background and objectiveNerve 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.MethodsGuinea 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.ResultsLymphocyte, 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).ConclusionsSH2-Bβ is expressed in AM of normal guinea pigs, and SH2-Bβ may participate in asthma pathogenesis through the NGF–TrkA signalling pathway.

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