Pan-neurotrophin receptor p75 contributes to neuronal hyperreactivity and airway inflammation in a murine model of experimental asthma.
Bronchial asthma represents a severe chronic inflammatory disease with increasing prevalence. The pathogenesis is characterized by complex neuroimmune dysregulation. Although the immunopathogenesis of the disease has been extensively studied, the nature of neuronal dysfunction still remains poorly understood. Recent data indicate that neurotrophins contribute to airway inflammation, broncho-obstruction and airway hyperresponsiveness. Using an established murine model of allergic bronchial asthma, the contribution of the pan-neurotrophin receptor p75(NTR) was defined. This receptor is expressed both in normal and asthmatic lungs and airways. Analysis of p75(NTR-/-) mice, as well as in vivo blocking of p75(NTR), revealed that airway inflammation is to a large extent dependent upon functional receptor expression. Furthermore, neuronal hyperreactivity depends entirely on this receptor. Based on these data, a novel molecular pathway in the neuroimmune pathogenesis of bronchial asthma could be defined.
Kerzel
Sebastian
S
Department of Clinical Chemistry and Molecular Diagnostics, Philipps-University Marburg, Marburg, Germany.
Päth
Günter
G
Nockher
Wolfgang A
WA
Quarcoo
David
D
Raap
Ulrike
U
Groneberg
David A
DA
Dinh
Q Thai
QT
Fischer
Axel
A
Braun
Armin
A
Renz
Harald
H
D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000502:physiology; D009474:Neurons / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012137:Respiratory System / Q000294:innervation; D013373:Substance P / Q000378:metabolism
D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D013373:Substance P; D010047:Ovalbumin