轻度哮喘患者骨形态发生蛋白受体的基础表达减少
2008/09/28
尽管对骨形态发生蛋白（BMP）信号转导在组织重塑中作用的认识日益提高，但BMP在哮喘气道中的表达及信号转导途径仍然未知。英国伦敦皇家学院的研究小组拟通过试验，测定哮喘患者和非哮喘对照组基础、抗原激发后BMP配体（BMP-2、BMP-4、BMP-7）及Ⅰ型、Ⅱ型受体（ALK-2、ALK-3、ALK-6和BMPRⅡ）的表达水平，并通过测定磷酸化Smad1/5水平来证实BMP信号途径的活化。
他们获取了15名特应性哮喘患者及6名非哮喘志愿者的支气管活检标本，通过免疫组化方法测定分析了基线点、抗原激发后24小时、7天的BMP配体及受体表达。
结果发现：在基线水平，哮喘及对照组的BMP配体表达无显著差异，但哮喘组ALK-2、ALK-6和BMPRⅡ等受体表达明显下调。抗原激发后，气道上皮的BMP-7水平显著而持续升高，炎症细胞侵润。同时，升高的磷酸化Smad1/5蛋白表达、ALK-2和ALK-6水平证实了信号转导活化。
由此得出结论：哮喘气道中BMP受体表达减少，阻止了气道的修复反应。抗原激发可提高调节性配体BMP-7的表达，激活BMP信号途径并提高受体表达，从而有助于炎症修复和控制。
（农英 卫生部中日友好医院呼吸内科 100029 摘译）
（Am J Respir Crit Care Med. 2008 May 15;177(10):1074-1081）
Basal Expression of Bone Morphogenetic Protein (BMP) Receptor is Reduced in Mild Asthma.
Kariyawasam HH, Xanthou G, Barkans J, Aizen M, Kay AB, Robinson DS.
Allergy and Clinical Immunology Section, Imperial College London, London, United Kingdom; Leukocyte Biology Section, Imperial College London, London, United Kingdom; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom.
RATIONALE: Despite increasing recognition of BMP signalling in tissue remodelling the expression pattern of ligands and signalling pathways remain undefined in the asthmatic airway.
OBJECTIVES: To determine expression of BMP ligands (BMP-2, 4 and 7) and Type I and Type II receptors (ALK-2, ALK-3, ALK-6 and BMPRII) as well as evidence for activation of BMP signalling via detection of phosphorylated (p)Smad1/5 expression in asthmatic airways at baseline (compared to non-asthmatic controls), and after allergen challenge.
METHODS: Bronchial biopsies were obtained from 6 non-asthmatic control volunteers, and 15 atopic asthmatics (median age 25 years, median FEV1% predicted 97%) at baseline, then at 24 hours and 7 days after allergen challenge. Expression of BMP ligands, receptors and signalling was analysed using immunohistochemistry.
RESULTS: BMP ligand expression did not differ between asthmatic and control airways at baseline. Compared to the normal airway there was significant down regulation of ALK- 2 (p=0.001), ALK-6 (p=0.0009) and BMPRII (p=0.009) expression in asthma. Allergen challenge was associated with marked and sustained up-regulation of BMP-7 in airway epithelium (p=0.017) and infiltrating inflammatory cells (p=0.071) (predominantly in eosinophils, but also CD4(+) T cells, mast cells and macrophages). Up-regulation of pSmad1/5 expression (p=0.031), ALK-2 (p=0.002) and ALK-6 (p<0.001) was observed indicating active signalling. CONCLUSION: BMP receptor expression is down-regulated in the asthmatic airway which may impede repair responses. Allergen provocation increases expression of the regulatory ligand BMP-7, activates BMP signalling and increases receptor expression all of which may contribute to repair and control of inflammation.
OBJECTIVES: To determine expression of BMP ligands (BMP-2, 4 and 7) and Type I and Type II receptors (ALK-2, ALK-3, ALK-6 and BMPRII) as well as evidence for activation of BMP signalling via detection of phosphorylated (p)Smad1/5 expression in asthmatic airways at baseline (compared to non-asthmatic controls), and after allergen challenge.
METHODS: Bronchial biopsies were obtained from 6 non-asthmatic control volunteers, and 15 atopic asthmatics (median age 25 years, median FEV1% predicted 97%) at baseline, then at 24 hours and 7 days after allergen challenge. Expression of BMP ligands, receptors and signalling was analysed using immunohistochemistry.
RESULTS: BMP ligand expression did not differ between asthmatic and control airways at baseline. Compared to the normal airway there was significant down regulation of ALK- 2 (p=0.001), ALK-6 (p=0.0009) and BMPRII (p=0.009) expression in asthma. Allergen challenge was associated with marked and sustained up-regulation of BMP-7 in airway epithelium (p=0.017) and infiltrating inflammatory cells (p=0.071) (predominantly in eosinophils, but also CD4(+) T cells, mast cells and macrophages). Up-regulation of pSmad1/5 expression (p=0.031), ALK-2 (p=0.002) and ALK-6 (p<0.001) was observed indicating active signalling. CONCLUSION: BMP receptor expression is down-regulated in the asthmatic airway which may impede repair responses. Allergen provocation increases expression of the regulatory ligand BMP-7, activates BMP signalling and increases receptor expression all of which may contribute to repair and control of inflammation.
上一篇：
促血管生成素-1可以阻止哮喘气道炎症及高反应性
下一篇：
腺苷-5-磷酸对哮喘的作用：气体交换和痰液细胞学反应
