Die Verstärkung der Frühphasereaktion des allergischen Asthma bronchiale durch den Nervenwachstumsfaktor NGF

Die allergische Frühphasereaktion, ein Kennzeichen des allergischen Asthma bronchiale, wird verursacht durch eine Allergen- und Immunglobulin E (IgE)- abhängige Mediatorfreisetzung aus Mastzellen. Es konnte bereits gezeigt werden, dass der Nervenwachstumsfaktor NGF (engl: Nerve Growth Factor) zu...

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Bibliographic Details
Main Author: Meents, Nina
Contributors: Renz, Harald (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2006
Online Access:PDF Full Text
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The allergic early-phase reaction, a hallmark of allergic bronchial asthma, is caused by allergen and immunglobulin E-dependent mediator release from mast cells. It was previously shown that nerve growth factor (NGF) contributes to acute airway inflammation. This study further investigates the role of NGF in the allergic early-phase reaction using a well-established mouse model of ovalbumin-induced allergic airway inflammation. Treatment of sensitized and aerosol challenged BALB/c mice with blocking anti-NGF antibodies inhibited allergen-induced early-phase reaction and suppressed airway inflammation. Transgenic mice constitutively overexpressing NGF in the airways (Clara-cell secretory protein promoter (CCSP)-NGF-tg) were employed and compared with wild-type animals. In sensitized and challenged CCSP-NGF-tg mice early-phase reaction, airway inflammation as well as percental relative increases in serotonin levels were augmented compared with wild-type mice, whereas serum immunglobulin E levels remained unaffected. Furthermore, CCSP-NGF-tg mice developed an increased reactivity of sensory neurons in response to inhaled capsaicin demonstrating NGF-mediated neuronal plasticity. In contrast, neither NGF nor anti-NGF treatment altered methacholine-induced airway hyperreactivity indicating no direct effect of NGF on the susceptability of airway smooth muscle cells. These data provide evidence for the functional role of NGF in the development of allergic early phase responses in the airways and the lung.