Apoptosis and loss of adhesion of bronchial epithelial cells in asthma.
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.
Trautmann
Axel
A
Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland. trautmann_a@klinik.uni-wuerzburg.de
Kruger
Katja
K
Akdis
Mubeccel
M
Muller-Wening
Dietrich
D
Akkaya
Ahmet
A
Brocker
Eva-B
EB
Blaser
Kurt
K
Akdis
Cezmi A
CA
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
D015820:Cadherins; D015815:Cell Adhesion Molecules; D019012:Integrin beta1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma