title: Augmentation of allergic early-phase reaction by nerve growth factor.
abstract: The allergic early-phase reaction, a hallmark of allergic bronchial asthma, is caused by allergen and immunoglobulin E-dependent mediator release from mast cells. It was previously shown that nerve growth factor (NGF) contributes to acute airway inflammation. This study further investigates the role of NGF in the allergic early-phase reaction using a well-established mouse model of ovalbumin-induced allergic airway inflammation. Treatment of sensitized and aerosol challenged BALB/c mice with blocking anti-NGF antibodies inhibited allergen-induced early-phase reaction and suppressed airway inflammation. Transgenic mice constitutively overexpressing NGF in the airways (Clara-cell secretory protein promoter [CCSP]-NGF-tg) were employed and compared with wild-type animals. In sensitized and challenged CCSP-NGF-tg mice, early-phase reaction, airway inflammation, as well as percental relative increases in serotonin levels were augmented compared with wild-type mice. These effects were paralleled by increased serotonin levels in the airways, whereas immunoglobulin E levels remained unaffected. Furthermore, CCSP-NGF-tg mice developed an increased reactivity of sensory neurons in response to inhaled capsaicin demonstrating NGF-mediated neuronal plasticity. These data provide evidence for the functional role of NGF in the development of allergic early phase responses in the airways and the lung.
authors.affiliation: Department of Clinical Chemistry and Molecular Diagnostic, University Hospital of Marburg, Marburg, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Päth
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
authors.forename: Nina
authors.initials: N
authors.lastname: Meents
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kerzel
authors.forename: David
authors.initials: D
authors.lastname: Quarcoo
authors.forename: Ulrike
authors.initials: U
authors.lastname: Raap
authors.forename: Gary W
authors.initials: GW
authors.lastname: Hoyle
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Nockher
authors.forename: Harald
authors.initials: H
authors.lastname: Renz
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology / Q000503:physiopathology; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D002211:Capsaicin / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006967:Hypersensitivity / Q000276:immunology* / Q000503:physiopathology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D009473:Neuronal Plasticity; D011401:Promoter Regions, Genetic; D012701:Serotonin / Q000378:metabolism
chemical_list: D000485:Allergens; D012701:Serotonin; D007073:Immunoglobulin E; D020932:Nerve Growth Factor; D002211:Capsaicin