Flow cytometric measurement of tumor necrosis factor-related apoptosis-inducing ligand and its receptors in gastric epithelium and infiltrating mucosal lymphocytes in Helicobacter pylori-associated gastritis.
BACKGROUND
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors have recently been reported to be responsible for apoptotic signaling molecules. However, little is known about TRAIL-mediated apoptosis in the human glandular stomach.


METHODS
Biopsies from 66 patients (28 Helicobacter pylori-negative, 38 H. pylori-positive) were investigated for phenotypic distribution of TRAIL and its receptors DR4/DR5 and DcR2 on mucosal epithelium, and infiltrating mucosal lymphocytes using flow cytometry. Apoptosis of the cells was examined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick and labeling (TUNEL). In addition, the phenotypic distribution of CD antigens on infiltrating major T- and B-lymphocytes were determined.


RESULTS
Membrane-bound TRAIL and its receptors were constitutively expressed in all patients with high levels in the gastric mucosal epithelium. In particular, these protein molecules were overexpressed in mucosal lymphocytes coupled with increased proportions of CD19+ B cells, and CD3+ T cells bearing CD8+CD11b- and CD4+CD62L- surface phenotypes in H. pylori-positive gastric mucosa. The frequencies of apoptotic epithelium and infiltrating lymphocytes in H. pylori-associated gastritis were significantly greater than those of H. pylori-negative normal mucosa (P < 0.01).


CONCLUSIONS
The present findings show that flow cytometric analysis is useful for detection of membrane-bound TRAIL and its receptors in gastric epithelium and infiltrating mucosal lymphocytes.
Koyama
Shohei
S
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. s-koyama@md.tsukuba.ac.jp
D000328:Adult; D000368:Aged; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism*; D005756:Gastritis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha