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


METHODS
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.
Ohara
Tadashi
T
Department of Internal Medicine, Tokyo Dental College, Chiba Hospital, Ichikawa General Hospital, Chiba, Japan. tohara@tdc.ac.jp
Morishita
Tetsuo
T
Suzuki
Hidekazu
H
Masaoka
Tatsuhiro
T
Ishii
Hiromasa
H
D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D001706:Biopsy; D053148:Caspase 3; D020169:Caspases / Q000235:genetics; D004386:Duodenum / Q000473:pathology; D053222:Fas Ligand Protein; D005753:Gastric Mucosa / Q000473:pathology; D015870:Gene Expression / Q000502:physiology; D053804:Granzymes; D016481:Helicobacter Infections / Q000235:genetics* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D009479:Neuropeptides / Q000235:genetics; D010437:Peptic Ulcer / Q000235:genetics* / Q000473:pathology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D019014:fas Receptor
C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D052899:Pore Forming Cytotoxic Proteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases