Nerve growth factor induces increased airway inflammation via a neuropeptide-dependent mechanism in a transgenic animal model of allergic airway inflammation.
BACKGROUND
Nerve growth factor (NGF) exerts an important functional impact on the pathogenesis of allergic diseases. Data obtained in animal models of allergic bronchial asthma indicate that NGF alters sensory nerve function and promotes allergic inflammation, bronchial hyper-reactivity, and airway obstruction.


OBJECTIVE
To further delineate the effects of NGF on airway inflammation, we employed a transgenic (tg) animal model of allergic inflammation and asthma.


METHODS
NGF-tg mice, which overexpress NGF in Clara cells of the airways, were compared with wild-type (wt) littermates regarding their ability to mount IgE-related airway inflammatory responses. Mice were sensitized intraperitoneally to ovalbumin (OVA) and locally challenged via the airways according to established protocols.


RESULTS
NGF-tg mice displayed enhanced levels of OVA-specific IgE antibody titres after repeated OVA aerosol exposure. In the airways, increased numbers of eosinophils were detected. These results were confirmed to be NGF specific, because similar results were obtained following local application of NGF into the airways of wt mice. The effect of NGF was partly mediated via neuropeptides, as treatment of OVA-sensitized NGF-tg mice with the dual neurokinin (NK) receptor NK-1/NK-2 antagonist partly prevented enhanced airway inflammation.


CONCLUSIONS
The present data indicate an important functional role of NGF in allergic airway inflammation and point to an involvement of tachykinins as mediators of NGF effects.
Quarcoo
D
D
Department of Clinical Chemistry and Molecular Diagnostics, University of Marburg, Germany.
Schulte-Herbrüggen
O
O
Lommatzsch
M
M
Schierhorn
K
K
Hoyle
G W
GW
Renz
H
H
Braun
A
A
D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D015848:Interleukin-5 / Q000097:blood; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009414:Nerve Growth Factors / Q000097:blood / Q000378:metabolism*; D010047:Ovalbumin; D010456:Peptides, Cyclic / Q000494:pharmacology; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000378:metabolism
D015848:Interleukin-5; D009414:Nerve Growth Factors; D010456:Peptides, Cyclic; D018039:Receptors, Tachykinin; D015320:Tachykinins; C075570:FK 224; D010047:Ovalbumin