© 2003 American Thoracic Society DOI: 10.1165/rcmb.4811 Pan-Neurotrophin Receptor p75 Contributes to Neuronal Hyperreactivity and Airway Inflammation in a Murine Model of Experimental AsthmaDepartment of Clinical Chemistry and Molecular Diagnostics, Philipps-University Marburg, Marburg; Fraunhofer Institute of Toxicology and Aerosol Research, Drug Research and Clinical Inhalation, Hannover; and Clinical Research Unit of Allergy, Charité School of Medicine, Humboldt-University Berlin, Germany Address correspondence to: Harald Renz, MD, Philipps-University Marburg, Department of Clinical Chemistry and Molecular Diagnostics; Central Laboratory Baldinger Strasse 35033 Marburg, Germany e-mail: renzh{at}post.med.uni-marburg.de 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 p75NTR was defined. This receptor is expressed both in normal and asthmatic lungs and airways. Analysis of p75NTR-/- mice, as well as in vivo blocking of p75NTR, 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.
Abbreviations: airway hyperresponsiveness, AHR • fetal calf serum, FCS • interleukin, IL • interferon, IFN • immunoglobulin, IgG • nerve growth factor, NGF • ovalbumin, OVA • phosphate-buffered saline, PBS • substance P, SP • time of break, TB • Tris-buffered saline, TBS • tyrosine kinase receptors, trk This article has been cited by other articles:
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