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Neurotrophins in allergic airway dysfunction: What the mouse model is teaching us

 
: Lommatzsch, M.; Braun, A.; Renz, H.

Sternberg, E.M. ; International Society for Neuroimmunomodulation -ISNIM-:
Neuroendocrine and neural regulation of autoimmune and inflammatory disease : Molecular, systems, and clinical insights. Contributions from the 5th International Congress of the International Society for NeuroImmunoModulation held on September 9-11, 2002 in Montpellier, France
New York/N.Y.: New York Academy of Sciences, 2003 (Annals of the New York Academy of Sciences 992)
ISBN: 1-573-31454-4
ISBN: 1-573-31455-2
pp.241-249
International Society for Neuroimmunomodulation (International Congress) <5, 2002, Montpellier>
English
Conference Paper, Journal Article
Fraunhofer ITEM ()
Neurotrophin; allergy; disease; animal model; Asthma; nerve growth factor

Abstract
Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are potent mediators of neuronal plasticity in the adult. There is increasing evidence that they regulate a variety of immune functions as well. Thus, neurotrophins are candidate molecules for neuroimmune interactions in allergic bronchial asthma, where elevated neurotrophin levels have been reported. In a mouse model of allergic airway inflammation we have identified macrophages and lymphocytes as additional cellular sources of NGF and BDNF in the inflamed lung. There was an unusual time course of BDNF in bronchoalveolar lavage fluid. BDNF levels peaked 1 week after the last allergen challenge, and did not correlate with the time course of the inflammatory response. In a series of experiments using blocking anti-NGF and anti-BDNF antibodies, we have shown that NGF specifically enhances inflammation and the allergic early-phase response. In contrast, BDNF influenced chronic airway obstruction and local neuronal hyperreactivity without affecting inflammation. Using transgenic mice overexpressing NGF in the airway epithelium, we have confirmed the data obtained from anti-NGF experiments. Allergen-challenged NGF overexpressors displayed a markedly augmented airway inflammation, early-phase response, and sensory irritation compared to wild-type mice. Studies with p75-NTR (-/-) knockout mice showed that these NGF effects are at least in part mediated by the low-affinity neurotrophin receptor. Thus, our experiments suggest that NGF and BDNF have a profound, but differential impact on allergic airway dysfunction.

: http://publica.fraunhofer.de/documents/N-17571.html