Braun Armin, Lommatzsch Marek, Neuhaus-Steinmetz Ulrich, Quarcoo David, Glaab Thomas, McGregor Gerard P, Fischer Axel, Renz Harald
Department of Immunology and Allergology, Fraunhofer Institute of Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, Hannover D-30625, Germany.
Br J Pharmacol. 2004 Feb;141(3):431-40. doi: 10.1038/sj.bjp.0705638. Epub 2004 Jan 12.
Brain-derived neurotrophic factor (BDNF) is a candidate molecule for mediating functional neuronal changes in allergic bronchial asthma. Recently, enhanced production of BDNF during allergic airway inflammation caused by infiltrating T-cells and macrophages as well as by resident airway epithelial cells has been described. It was the aim of this study to investigate the effect of enhanced BDNF levels on lung function and airway inflammation in a mouse model of allergic inflammation. Ovalbumin-sensitised BALB/c mice were challenged in two consecutive allergen challenges. Prior to the challenge, the mice were treated with either anti-BDNF antibodies or isotype-matched control antibodies. Airway responsiveness to methacholine, capsaicin and electric field stimulation, as well as airway inflammation and chronic airway obstruction 1 week after the last allergen challenge were assessed. Anti-BDNF blocked enhanced reactivity in response to capsaicin, but not airway smooth muscle hyper-reactivity in vivo. Furthermore, persistent airway obstruction, as observed 1 week after the last allergen challenge, was to a large extent prevented by anti-BDNF treatment. In vitro, BDNF and anti-BDNF treatment had a profound effect on local neuronal hyper-reactivity, as shown by electric field stimulation experiments. In contrast, neither BDNF nor anti-BDNF treatment affected airway inflammation. Our data indicate that development of allergen-induced neuronal hyper-reactivity in mice is partially mediated by BDNF. British Journal of Pharmacology (2004) 141, 431-440. doi:10.1038/sj.bjp.0705638
脑源性神经营养因子（BDNF）是介导过敏性支气管哮喘中功能性神经元变化的候选分子。最近，有研究描述了在由浸润的T细胞和巨噬细胞以及气道上皮驻留细胞引起的过敏性气道炎症期间，BDNF的产生会增强。本研究的目的是在过敏性炎症小鼠模型中研究BDNF水平升高对肺功能和气道炎症的影响。用卵清蛋白致敏的BALB/c小鼠接受连续两次变应原激发。在激发前，小鼠用抗BDNF抗体或同型对照抗体治疗。评估了对乙酰甲胆碱、辣椒素和电场刺激的气道反应性，以及最后一次变应原激发后1周的气道炎症和慢性气道阻塞情况。抗BDNF可阻断对辣椒素的反应性增强，但不能阻断体内气道平滑肌的高反应性。此外，在最后一次变应原激发后1周观察到的持续性气道阻塞在很大程度上可通过抗BDNF治疗得到预防。在体外，电场刺激实验表明，BDNF和抗BDNF治疗对局部神经元高反应性有深远影响。相比之下，BDNF和抗BDNF治疗均未影响气道炎症。我们的数据表明，小鼠变应原诱导的神经元高反应性的发展部分由BDNF介导。《英国药理学杂志》（2004年）141卷，431 - 440页。doi:10.1038/sj.bjp.0705638
