title: T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma.
abstract: BACKGROUND
  Asthma is an inflammatory airway disease associated with an infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (ECs).
  
  
  OBJECTIVE
  Shedding of bronchial ECs is characterized by loss of the normal bronchial pseudostratified epithelium and the maintenance of a few basal cells on a thickened basement membrane. The aim of this study was to investigate whether, and by which mechanism, T cells and eosinophils can cause damage to airway ECs.
  
  
  METHODS
  Bronchial ECs, cultured and exposed to cytokines, eosinophil cationic protein, activated T cells, and eosinophils were studied for the expression of apoptosis receptors (flow cytometry, immunoblotting, and RNA expression) and for the susceptibility for undergoing apoptosis. In addition, bronchial biopsy specimens from patients with asthma were evaluated for EC apoptosis.
  
  
  RESULTS
  We demonstrate herein that the respiratory epithelium is an essential target of the inflammatory attack by T cells and eosinophils. Bronchial ECs underwent cytokine-induced cell death with DNA fragmentation and morphologic characteristics of apoptosis mediated by activated T cells and eosinophils. T cell- and eosinophil-induced EC apoptosis was blocked by inhibition of IFN-alpha and TNF-alpha; the Fas ligand-Fas pathway appears to be less important. Recombinant eosinophil cationic protein induced mainly necrosis of ECs. Furthermore, we demonstrated in situ apoptotic features of ECs in bronchial biopsy specimens of asthmatic patients.
  
  
  CONCLUSIONS
  T cell- and eosinophil-induced apoptosis represents a key pathogenic event leading to EC shedding in asthma.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
authors.forename: Axel
authors.initials: A
authors.lastname: Trautmann
authors.forename: Peter
authors.initials: P
authors.lastname: Schmid-Grendelmeier
authors.forename: Katja
authors.initials: K
authors.lastname: Krüger
authors.forename: Reto
authors.initials: R
authors.lastname: Crameri
authors.forename: Mübeccel
authors.initials: M
authors.lastname: Akdis
authors.forename: Ahmet
authors.initials: A
authors.lastname: Akkaya
authors.forename: Eva-B
authors.initials: EB
authors.lastname: Bröcker
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 / Q000276:immunology / Q000503:physiopathology*; D001706:Biopsy; D001980:Bronchi / Q000276:immunology / Q000473:pathology*; D002478:Cells, Cultured; D004804:Eosinophils / Q000502:physiology*; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology*; D053222:Fas Ligand Protein; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D007371:Interferon-gamma