Airway epithelial cells produce neurotrophins and promote the survival of eosinophils during allergic airway inflammation.
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-1beta, TNF-alpha, and T(H)2 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.


CONCLUSIONS
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.


CONCLUSIONS
Attenuating the release of inflammatory mediators from the activated airway epithelium will become an important strategy to disrupt the pathogenesis of chronic allergic asthma.
Hahn
Christian
C
Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the University, Philipps-University Marburg, Germany.
Islamian
Ariyan Pirayesh
AP
Renz
Harald
H
Nockher
Wolfgang Andreas
WA
D000818:Animals; D001249:Asthma / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002470:Cell Survival; D016207:Cytokines / Q000494:pharmacology; D004804:Eosinophils / Q000473:pathology* / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020917:Receptor, trkA / Q000096:biosynthesis; D020813:Receptor, trkB / Q000096:biosynthesis; D012130:Respiratory Hypersensitivity / Q000473:pathology* / Q000503:physiopathology*; D012137:Respiratory System / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*
D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D018836:Inflammation Mediators; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020917:Receptor, trkA; D020813:Receptor, trkB