Distinct patterns of mucosal apoptosis in H pylori-associated gastric ulcer are associated with altered FasL and perforin cytotoxic pathways

作     者：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 

作者机构：Departamento de Clínica Médica Instituto de Ciências Biomédicas Universidade Federal do Rio de Janeiro 21941-590 Brazil Laboratório Multidisciplinar de Pesquisa e Departamento de Anatomia Patologica Instituto de Ciências Biomédicas Universidade Federal do Rio de Janeiro 21941-590 Brazil Hospital Universitário Clementino Fraga Filho Departamento de Histologia e Embriologia Instituto de Ciências Biomédicas Universidade Federal do Rio de Janeiro 21941-590 Brazil Laboratório de Imunologia Celular Instituto de Ciências Biomédicas Universidade Federal do Rio de Janeiro 21941-590 Brazil 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2006年第12卷第38期

页      面：6133-6141页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by grants from the Brazilian Research Council/CNPq  FAPERJ  and Fundao José Bonifácio/FUJB 

主　　题：Gastric ulcer H pylori Apoptosis Fas receptor Fas ligand Perforin 

摘      要：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 immunoper- oxidase, 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 eradi- cation 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 macro- phage 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 enhance- ment 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.