Airway epithelial cells produce neurotrophins and promote the survival of eosinophils during allergic airway inflammation - 17/08/11
Reprint requests: Wolfgang Andreas Nockher, MD, MSc, Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the University, Baldingerstrasse 35033 Marburg, Germany.Marburg, Germany
Abstract |
Background |
Eosinophil-epithelial cell interactions make a major contribution to asthmatic airway inflammation. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and other members of the neurotrophin family, originally defined as a class of neuronal growth factors, are now recognized to support the survival and activation of immune cells. Neurotrophin levels are increased in bronchoalveolar lavage fluid during allergic asthma.
Objective |
We sought to investigate the role of neurotrophins as inflammatory mediators in eosinophil-epithelial cell interactions during the allergic immune response.
Methods |
Neurotrophin expression in the lung was investigated by means of immunohistochemistry and ELISA in a mouse model of chronic experimental asthma. Coculture experiments were performed with airway epithelial cells and bronchoalveolar lavage fluid eosinophils.
Results |
Neurotrophin levels increased continuously during chronic allergic airway inflammation, and airway epithelial cells were the major source of NGF and BDNF within the inflamed lung. Epithelial neurotrophin production was upregulated by IL-1β, TNF-⍺, and TH2 cytokines. Lung eosinophils expressed the BDNF and NGF receptors tropomyosin-related kinase (Trk) A and TrkB, and coculture with airway epithelial cells resulted in enhanced epithelial neurotrophin production, as well as in prolonged survival of eosinophils. Eosinophil survival was completely abolished in the presence of the neurotrophin receptor Trk antagonist K252a.
Conclusion |
During allergic inflammation, airway epithelial cells express increased amounts of NGF and BDNF that promote the survival of tissue eosinophils. Controlling epithelial neurotrophin production might be an important therapeutic target to prevent allergic airway eosinophilia.
Clinical implications |
Attenuating the release of inflammatory mediators from the activated airway epithelium will become an important strategy to disrupt the pathogenesis of chronic allergic asthma.
Le texte complet de cet article est disponible en PDF.Key words : Allergy, asthma, neurotrophin, nerve growth factor, brain-derived neutrotrophic factor, eosinophils, survival, airway epithelium
Abbreviations used : 7-AAD, BALF, BDNF, MTEC, NGF, NT-3, OVA, Trk
Plan
| Supported by grants from the German National Science Foundation, Deutsche Forschungsgemeinschaft (Transregio 22, Projekt A9), and Stiftung für Pathobiochemie und Molekulare Diagnostik, DGKL. Disclosure of potential conflict of interest: The authors have declared they have no conflict of interest. |
Vol 117 - N° 4
P. 787-794 - avril 2006 Retour au numéro
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