Perforin and granzyme B of cytotoxic T lymphocyte mediate apoptosis irrespective of Helicobacter pylori infection: possible act as a trigger of peptic ulcer formation

BACKGROUND/AIMS: The perforin/granzyme and Fas/Fas ligand pathways are two known major pathways of cytotoxic T lymphocyte-mediated apoptosis. We designed a clinical study to examine whether cytotoxic T lymphocyte-mediated apoptosis associated with peptic ulcer formation may occur via either or both of these two pathways. METHODOLOGY: Mucosal biopsy specimens were obtained endoscopically from the marginal zone of active stage gastric and duodenal ulcers in patients with or without Helicobacter pylori infection. RT-PCR, immunoblotting and immunohistochemistry were used to study the samples for the expression of apoptotic cells, perforin, granzyme B, Fas, Fas ligand and caspase 3. RESULTS: Apoptotic cells (Tunnel positive cells) appeared in the marginal zone of gastric and duodenal ulcers with and without H. pylori infection. Perforin/granzyme B and caspase 3 were expressed consistently, however Fas ligand was not. Furthermore, the immunohistochemical findings demonstrated apoptotic changes of target cells caused by perforin/granzyme B. CONCLUSIONS: These results suggest that the main pathway of cytotoxic T lymphocyte-mediated apoptosis in peptic ulcer formation is the perforin/granzyme pathway irrespective of H. pylori infection.