Augmentation of allergic early-phase reaction by nerve growth factor.
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.
Päth
Günter
G
Department of Clinical Chemistry and Molecular Diagnostic, University Hospital of Marburg, Marburg, Germany.
Braun
Armin
A
Meents
Nina
N
Kerzel
Sebastian
S
Quarcoo
David
D
Raap
Ulrike
U
Hoyle
Gary W
GW
Nockher
Wolfgang A
WA
Renz
Harald
H
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
D000485:Allergens; D012701:Serotonin; D007073:Immunoglobulin E; D020932:Nerve Growth Factor; D002211:Capsaicin