Kerzel Sebastian, Päth Günter, Nockher Wolfgang A, Quarcoo David, Raap Ulrike, Groneberg David A, Dinh Q Thai, Fischer Axel, Braun Armin, Renz Harald
Department of Clinical Chemistry and Molecular Diagnostics, Philipps-University Marburg, Marburg, Germany.
Am J Respir Cell Mol Biol. 2003 Feb;28(2):170-8. doi: 10.1165/rcmb.4811.
Bronchial asthma represents a severe chronic inflammatory disease with increasing prevalence. The pathogenesis is characterized by complex neuroimmune dysregulation. Although the immunopathogenesis of the disease has been extensively studied, the nature of neuronal dysfunction still remains poorly understood. Recent data indicate that neurotrophins contribute to airway inflammation, broncho-obstruction and airway hyperresponsiveness. Using an established murine model of allergic bronchial asthma, the contribution of the pan-neurotrophin receptor p75(NTR) was defined. This receptor is expressed both in normal and asthmatic lungs and airways. Analysis of p75(NTR-/-) mice, as well as in vivo blocking of p75(NTR), revealed that airway inflammation is to a large extent dependent upon functional receptor expression. Furthermore, neuronal hyperreactivity depends entirely on this receptor. Based on these data, a novel molecular pathway in the neuroimmune pathogenesis of bronchial asthma could be defined.
支气管哮喘是一种患病率不断上升的严重慢性炎症性疾病。其发病机制的特点是复杂的神经免疫失调。尽管该疾病的免疫发病机制已得到广泛研究，但神经元功能障碍的本质仍知之甚少。最近的数据表明，神经营养因子会导致气道炎症、支气管阻塞和气道高反应性。利用已建立的过敏性支气管哮喘小鼠模型，确定了泛神经营养因子受体p75（NTR）的作用。该受体在正常和哮喘的肺及气道中均有表达。对p75（NTR-/-）小鼠的分析以及p75（NTR）的体内阻断显示，气道炎症在很大程度上依赖于功能性受体的表达。此外，神经元的高反应性完全依赖于该受体。基于这些数据，可以确定支气管哮喘神经免疫发病机制中的一条新分子途径。
