title: Pulmonary distribution, regulation, and functional role of Trk receptors in a murine model of asthma.
abstract: BACKGROUND
  Neurotrophins have been implicated in the pathogenesis of asthma because of their ability to promote hyperreactivity of sensory neurons and to induce airway inflammation. Hyperreactivity of sensory nerves is one key mechanism of airway hyperreactivity that is defined as an abnormal reactivity of the airways to unspecific stimuli, such as cold air and cigarette smoke. Neurotrophins use a dual-receptor system consisting of Trk receptor tyrosine kinases and the structurally unrelated p75 neurotrophin receptor.
  
  
  OBJECTIVE
  The aim of this study was to characterize the distribution, allergen-dependent regulation, and functional relevance of the Trk receptors in allergic asthma.
  
  
  METHODS
  BALB/c mice were sensitized to ovalbumin. After provocation with ovalbumin or vehicle aerosol, respectively, Trk receptor expression was analyzed in lung tissue by means of fluorescence microscopy and quantitative RT-PCR. To assess the functional relevance of Trk receptors in asthma, we tested the effects of the intranasally administered pan-Trk receptor decoy REN1826. Allergic airway inflammation was quantified and lung function was measured by using head-out body plethysmography.
  
  
  RESULTS
  Trk receptors were expressed in neurons, airway smooth muscle cells, and cells of the inflammatory infiltrate surrounding the bronchi and upregulated after allergen challenge. Local application of REN1826 reduced IL-4 and IL-5 cytokine levels but had no effect on IL-13 levels or the cellular composition of bronchoalveolar lavage fluid cells. Furthermore, REN1826 decreased broncho-obstruction in response to sensory stimuli, indicating a diminished hyperreactivity of sensory nerves, but did not influence airway smooth muscle hyperreactivity in response to methacholine.
  
  
  CONCLUSIONS
  These results emphasize the important role of Trk receptor signaling in the development of asthma.
  
  
  CONCLUSIONS
  Our data indicate that blocking of Trk receptor signaling might reduce asthma symptoms.
authors.affiliation: Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Nassenstein
authors.forename: David
authors.initials: D
authors.lastname: Dawbarn
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pollock
authors.forename: Shelley Jane
authors.initials: SJ
authors.lastname: Allen
authors.forename: Veit Johannes
authors.initials: VJ
authors.lastname: Erpenbeck
authors.forename: Emma
authors.initials: E
authors.lastname: Spies
authors.forename: Norbert
authors.initials: N
authors.lastname: Krug
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
mesh_terms: D000485:Allergens / Q000502:physiology; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008168:Lung / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020812:Receptor, trkC / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D000485:Allergens; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC