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SH2-B beta expression in alveolar macrophages in BAL fluid of asthmatic guinea pigs and its role in NGF-TrkA-mediated asthma.
Respirology. 2009 Jan; 14(1):60-8.R

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-B beta, a TrkA-binding protein, modulates the NGF signalling pathway. In this study, SH2-B beta 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-B beta 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-B beta, anti-NGF and anti-TrkA antibodies were administered and AM were isolated from BAL fluid to assess SH2-B beta expression using an immunofluorescence assay. SH2-B beta and TrkA protein expression were determined by western blotting, IL-1 beta 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-B beta 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-B beta is expressed in AM of normal guinea pigs, and SH2-B beta may participate in asthma pathogenesis through the NGF-TrkA signalling pathway.

Authors+Show Affiliations

Institute of Respiratory Diseases, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19144050

Citation

Li, Li, et al. "SH2-B Beta Expression in Alveolar Macrophages in BAL Fluid of Asthmatic Guinea Pigs and Its Role in NGF-TrkA-mediated Asthma." Respirology (Carlton, Vic.), vol. 14, no. 1, 2009, pp. 60-8.
Li L, Kong L, Fang X, et al. SH2-B beta expression in alveolar macrophages in BAL fluid of asthmatic guinea pigs and its role in NGF-TrkA-mediated asthma. Respirology. 2009;14(1):60-8.
Li, L., Kong, L., Fang, X., Jiang, C., Wang, Y., Zhong, Z., Sun, Q., Gu, G., Zheng, D., Meng, R., & Kang, J. (2009). SH2-B beta expression in alveolar macrophages in BAL fluid of asthmatic guinea pigs and its role in NGF-TrkA-mediated asthma. Respirology (Carlton, Vic.), 14(1), 60-8. https://doi.org/10.1111/j.1440-1843.2008.01417.x
Li L, et al. SH2-B Beta Expression in Alveolar Macrophages in BAL Fluid of Asthmatic Guinea Pigs and Its Role in NGF-TrkA-mediated Asthma. Respirology. 2009;14(1):60-8. PubMed PMID: 19144050.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SH2-B beta expression in alveolar macrophages in BAL fluid of asthmatic guinea pigs and its role in NGF-TrkA-mediated asthma. AU - Li,Li, AU - Kong,Lingfei, AU - Fang,Xiubin, AU - Jiang,Changlin, AU - Wang,Yating, AU - Zhong,Zhaoshuang, AU - Sun,Qiyu, AU - Gu,Guozhong, AU - Zheng,Dongqing, AU - Meng,Rui, AU - Kang,Jian, PY - 2009/1/16/entrez PY - 2009/1/16/pubmed PY - 2009/5/9/medline SP - 60 EP - 8 JF - Respirology (Carlton, Vic.) JO - Respirology VL - 14 IS - 1 N2 - 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-B beta, a TrkA-binding protein, modulates the NGF signalling pathway. In this study, SH2-B beta 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-B beta 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-B beta, anti-NGF and anti-TrkA antibodies were administered and AM were isolated from BAL fluid to assess SH2-B beta expression using an immunofluorescence assay. SH2-B beta and TrkA protein expression were determined by western blotting, IL-1 beta 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-B beta 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-B beta is expressed in AM of normal guinea pigs, and SH2-B beta may participate in asthma pathogenesis through the NGF-TrkA signalling pathway. SN - 1440-1843 UR - https://www.unboundmedicine.com/medline/citation/19144050/SH2_B_beta_expression_in_alveolar_macrophages_in_BAL_fluid_of_asthmatic_guinea_pigs_and_its_role_in_NGF_TrkA_mediated_asthma_ L2 - https://doi.org/10.1111/j.1440-1843.2008.01417.x DB - PRIME DP - Unbound Medicine ER -