Addresss fro correspondence: Marek Lommatzsch, M.D., Department of Pneumology, University of Rostock, Ernst-Heydeman-Str. 6, 18055 Rostock, Germany. Voice: 0049-381-494-7461; fax: 0049-381-494-7392.
marek.lommatzsch{at}med.uni-rostock.de
Ann. N.Y. Acad. Sci. 992: 241-249 (2003).
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.
