H Pylori
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 14, 2006; 12(38): 6133-6141
Published online Oct 14, 2006. doi: 10.3748/wjg.v12.i38.6133
Distinct patterns of mucosal apoptosis in H pylori-associated gastric ulcer are associated with altered FasL and perforin cytotoxic pathways
Heitor SP Souza, Marcelo S Neves, Celeste CS Elia, Claudio JA Tortori, Ilana Dines, Cesonia A Martinusso, Kalil Madi, Leonardo Andrade, Morgana TL Castelo-Branco
Heitor SP Souza, Marcelo S Neves, Celeste CS Elia, Claudio JA Tortori, Ilana Dines, Cesonia A Martinusso, Departamento de Clínica Médica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-590, Brazil
Kalil Madi, Laboratório Multidisciplinar de Pesquisa, e Departamento de Anatomia Patologica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-590, Brazil
Leonardo Andrade, Hospital Universitário Clementino Fraga Filho; Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-590, Brazil
Morgana TL Castelo-Branco, Laboratório de Imunologia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-590, Brazil
Supported by grants from the Brazilian Research Council/CNPq, FAPERJ, and Fundação José Bonifácio/FUJB
Correspondence to: Heitor SP Souza, 9500 Euclid Avenue NC2-119-Pathobiology, Cleveland Clinic Foundation, Cleveland, Ohio, 44915, United States. desouzh@ccf.org
Telephone: +1-216-4454915
Received: December 29, 2005
Revised: June 8, 2006
Accepted: June 14, 2006
Published online: October 14, 2006
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Gastric ulcer, H pylori, Apoptosis, Fas receptor, Fas ligand, Perforin