title: Apoptosis and loss of adhesion of bronchial epithelial cells in asthma.
abstract: BACKGROUND
  Asthma is an inflammatory airway disease associated with infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (EC). We have recently shown that T cells and eosinophils cooperate in inducing bronchial EC apoptosis in asthma through secretion of IFN-gamma and TNF-alpha. Since EC shedding is a histologic hallmark of asthma, the intercellular junction of EC may be a target of pro-inflammatory cytokines.
  
  
  METHODS
  Bronchial EC, cultured and exposed to IFN-gamma and TNF-alpha, were studied for the expression of adhesion molecules and apoptosis. In addition, the epithelial layer of bronchial biopsies from asthma patients was evaluated for apoptosis, shedding, and expression of adhesion molecules.
  
  
  RESULTS
  We demonstrate that the induction of EC apoptosis is accompanied by loss of E-cadherin. In situ examination of E-cadherin in asthma revealed a reduction in its expression on EC membranes. In contrast, the in vitro and in vivo expression of beta1-integrins and intercellular adhesion molecule-1 (ICAM-1) increased on EC during asthmatic airway inflammation.
  
  
  CONCLUSIONS
  Loss of cadherin-mediated intercellular adhesion and apoptosis could account for fragility and shedding of EC in asthma, especially since this occurs between columnar and basal EC.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland. trautmann_a@klinik.uni-wuerzburg.de
authors.forename: Axel
authors.initials: A
authors.lastname: Trautmann
authors.forename: Katja
authors.initials: K
authors.lastname: Kruger
authors.forename: Mubeccel
authors.initials: M
authors.lastname: Akdis
authors.forename: Dietrich
authors.initials: D
authors.lastname: Muller-Wening
authors.forename: Ahmet
authors.initials: A
authors.lastname: Akkaya
authors.forename: Eva-B
authors.initials: EB
authors.lastname: Brocker
authors.forename: Kurt
authors.initials: K
authors.lastname: Blaser
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
mesh_terms: D017209:Apoptosis; D001249:Asthma / Q000473:pathology*; D001980:Bronchi / Q000276:immunology / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019012:Integrin beta1 / Q000032:analysis / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D019012:Integrin beta1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma