Lommatzsch Marek, Schloetcke Katharina, Klotz Jens, Schuhbaeck Katharina, Zingler Doerte, Zingler Christiana, Schulte-Herbrüggen Olaf, Gill Hartmut, Schuff-Werner Peter, Virchow Johann Christian
Department of Pneumology and Institute of Clinical Chemistry and Pathobiochemistry, University of Rostock, Rostock, Germany.
Am J Respir Crit Care Med. 2005 Jan 15;171(2):115-20. doi: 10.1164/rccm.200406-758OC. Epub 2004 Oct 29.
Brain-derived neurotrophic factor (BDNF), a key mediator of neuronal plasticity, contributes to airway obstruction and hyperresponsiveness in a model of allergic asthma. BDNF is stored in human platelets and circulates in human plasma, but the significance of BDNF in this compartment is poorly understood. We investigated the relationship between platelet and plasma BDNF levels and pulmonary function in a cohort of 26 adult patients with recently diagnosed allergic asthma. BDNF levels in serum, platelets, and plasma were significantly increased in participants with asthma, as compared with 26 age- and sex-matched control subjects. In steroid-naive patients, but not in patients using inhaled corticosteroids, enhanced platelet BDNF levels correlated with parameters of airway obstruction and airway hyperresponsiveness to histamine. Experiments with activated peripheral blood mononuclear cells revealed that corticosteroids such as fluticasone effectively suppress BDNF secretion. In conclusion, we demonstrate that enhanced platelet BDNF is associated with airflow limitation and airway hyperresponsiveness in asthma. In addition, we provide evidence that corticosteroids suppress BDNF production by activated immune cells.
脑源性神经营养因子(BDNF)是神经元可塑性的关键调节因子,在过敏性哮喘模型中可导致气道阻塞和高反应性。BDNF储存于人体血小板中并在血浆中循环,但人们对该部分BDNF的意义了解甚少。我们在26例近期诊断为过敏性哮喘的成年患者队列中,研究了血小板和血浆BDNF水平与肺功能之间的关系。与26名年龄和性别匹配的对照受试者相比,哮喘患者血清、血小板和血浆中的BDNF水平显著升高。在未使用类固醇的患者中,而非使用吸入性皮质类固醇的患者中,血小板BDNF水平升高与气道阻塞参数及气道对组胺的高反应性相关。对活化外周血单个核细胞进行的实验表明,诸如氟替卡松等皮质类固醇可有效抑制BDNF分泌。总之,我们证明血小板BDNF升高与哮喘中的气流受限和气道高反应性相关。此外,我们提供证据表明皮质类固醇可抑制活化免疫细胞产生BDNF。