Nerve growth factor induces increased airway inflammation via a neuropeptide-dependent mechanism in a transgenic animal model of allergic airway inflammation.

Abstract

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.

CONCLUSION:

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.

• Authors: D Quarcoo, O Schulte-Herbrüggen, M Lommatzsch, K Schierhorn, G W Hoyle, H Renz, A Braun
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 34 Issue 7 Pg. 1146-51 (Jul 2004) ISSN: 0954-7894 [Print] England
• PMID: 15248864 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-5
• Nerve Growth Factors
• Peptides, Cyclic
• Receptors, Tachykinin
• Tachykinins
• FK 224
• Ovalbumin

Topics

• Animals
• Asthma (immunology)
• Bronchial Hyperreactivity
• Eosinophils (immunology)
• Humans
• Interleukin-5 (blood)
• Leukocyte Count
• Lung (immunology)
• Mice
• Mice, Transgenic
• Models, Animal
• Nerve Growth Factors (blood, metabolism)
• Ovalbumin
• Peptides, Cyclic (pharmacology)
• Receptors, Tachykinin (antagonists & inhibitors)
• Tachykinins (metabolism)