title: Local increase in the number of mast cells and expression of nerve growth factor in the bronchus of asthmatic patients after repeated inhalation of allergen at low-dose.
abstract: BACKGROUND
  Repeated inhalation of allergen at low-dose induces an increase in bronchial hyper-responsiveness, without any associated symptom. The concomitant events in the bronchus have not been described.
  
  
  OBJECTIVE
  We have studied the dynamic number of mast cells in the airways of patients with mild asthma before and after repeated inhalation of allergen at low-dose and the expression of nerve growth factor (NGF), which is reported to promote growth and survival of mast cells.
  
  
  METHODS
  Twelve patients with mild asthma to cat allergen were enrolled at random in a blind placebo-controlled study, and submitted to repeated low-dose allergen exposure (1/5 of the provocative dose). Mast cells were immunolocalized using an antibody against mast cell tryptase. NGF and its high affinity receptor, TrkA, were immunolocalized using anti-NGF and anti-TrkA antibodies, respectively. NGF mRNA was quantified by competitive polymerase chain reaction (PCR) after reverse transcription of total RNA extracted from bronchial biopsy. NGF protein levels were measured by ELISA in bronchoalveolar lavage (BAL) fluid.
  
  
  RESULTS
  Bronchial mast cell number was increased significantly after allergen exposure as compared with before. NGF expression in the bronchus was immunolocalized mainly to epithelial cells, but also to fibroblasts, blood vessels, and a few infiltrated cells. NGF mRNA levels in bronchial biopsies were increased significantly after allergen exposure. The high affinity receptor for NGF, TrkA, was immunolocalized to the infiltrated mast cell membrane.
  
  
  CONCLUSIONS
  Our study shows that the increase in the number of mast cells and in the expression of NGF induced by allergen exposure in the bronchus of asthmatic patients is occurring before the onset of symptoms. In addition, our finding of the presence of the TrkA receptor on the membrane of the infiltrated mast cell in situ brings evidence of the mast cell as a target cell for the growth factor activity of NGF in the airways in asthma.
authors.affiliation: INSERM U 425, Université Louis Pasteur, Faculté de Pharmacie, BP 24, 67401 Illkirch Cedex, France.
authors.forename: O
authors.initials: O
authors.lastname: Kassel
authors.forename: F
authors.initials: F
authors.lastname: de Blay
authors.forename: C
authors.initials: C
authors.lastname: Duvernelle
authors.forename: C
authors.initials: C
authors.lastname: Olgart
authors.forename: D
authors.initials: D
authors.lastname: Israel-Biet
authors.forename: P
authors.initials: P
authors.lastname: Krieger
authors.forename: L
authors.initials: L
authors.lastname: Moreau
authors.forename: C
authors.initials: C
authors.lastname: Muller
authors.forename: G
authors.initials: G
authors.lastname: Pauli
authors.forename: N
authors.initials: N
authors.lastname: Frossard
mesh_terms: D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001706:Biopsy; D001980:Bronchi / Q000737:chemistry* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002415:Cats; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008407:Mast Cells / Q000737:chemistry / Q000502:physiology*; D020932:Nerve Growth Factor / Q000502:physiology*; D012333:RNA, Messenger / Q000502:physiology; D020917:Receptor, trkA / Q000502:physiology
chemical_list: D000485:Allergens; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D020917:Receptor, trkA