title: Distinct patterns of mucosal apoptosis in H pylori-associated gastric ulcer are associated with altered FasL and perforin cytotoxic pathways.
abstract: OBJECTIVE
  To analyze the level of apoptosis in different mucosal compartments and the differential expression of Fas/Fas-ligand and perforin in H pylori-associated gastric ulcer.
  
  
  METHODS
  Antral specimens from patients with H pylori-related active gastric ulcer (GU), H pylori-related gastritis, and non-infected controls were analysed for densities and distribution of apoptotic cells determined by the TdT-mediated dUDP-biotin nick-end-labelling method. GU patients were submitted to eradication therapy with follow-up biopsy after 60 d. Fas, FasL, and perforin-expressing cells were assessed by immunoperoxidase, and with anti-CD3, anti-CD20 and anti-CD68 by double immunofluorescence and confocal microscopy. Quantitative analysis was performed using a computer-assisted image analyser.
  
  
  RESULTS
  H pylori-infected antrum showed greater surface epithelial apoptosis which decreased after eradication therapy. In the lamina propria, higher rates of mononuclear cell apoptosis were observed in H pylori-gastritis. Co-expression of Fas with T-cell and macrophage markers was reduced in GU. FasL- and perforin-expressing cells were increased in H pylori-infection and correlated with epithelial apoptosis. Perforin-expressing cells were also increased in GU compared with H pylori-gastritis.
  
  
  CONCLUSIONS
  Epithelial apoptosis is increased in H pylori-infection and correlates to FasL- and perforin-expression by T cells. Expression of perforin is correlated with the tissue damage, and may represent the enhancement of a distinct cytotoxic pathway in GU. Increased expression of FasL not paralleled by Fas on T-cells and macrophages may indicate a reduced susceptibility to the Fas/FasL-mediated apoptosis of lymphoid cells in H pylori-infection.
authors.affiliation: Departamento de Clínica Médica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-590, Brazil. desouzh@ccf.org
authors.forename: Heitor-S-P
authors.initials: HS
authors.lastname: Souza
authors.forename: Marcelo-S
authors.initials: MS
authors.lastname: Neves
authors.forename: Celeste-C-S
authors.initials: CC
authors.lastname: Elia
authors.forename: Claudio-J-A
authors.initials: CJ
authors.lastname: Tortori
authors.forename: Ilana
authors.initials: I
authors.lastname: Dines
authors.forename: Cesonia-A
authors.initials: CA
authors.lastname: Martinusso
authors.forename: Kalil
authors.initials: K
authors.lastname: Madi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Andrade
authors.forename: Morgana-T-L
authors.initials: MT
authors.lastname: Castelo-Branco
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D016481:Helicobacter Infections / Q000503:physiopathology; D016480:Helicobacter pylori; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism*; D013276:Stomach Ulcer / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin