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. 1999 Apr;44(4):456–462. doi: 10.1136/gut.44.4.456

Role of apoptosis induced by Helicobacter pylori infection in the development of duodenal ulcer

K Kohda 1, K Tanaka 1, Y Aiba 1, M Yasuda 1, T Miwa 1, Y Koga 1
PMCID: PMC1727459  PMID: 10075950

Abstract

BACKGROUND—Helicobacter pylori affects gastric epithelium integrity by acceleration of apoptosis. However, it remains unclear what product of the bacteria causes apoptosis, or whether or not the apoptosis is involved in the development of ulcers. 
AIMS—To elucidate the factor from H pylori that causes acceleration of apoptosis and the role of apoptosis in the development of duodenal ulcer in H pylori infection. 
PATIENTS—Five H pylori negative healthy volunteers, 47 H pylori positive patients with duodenal ulcer, and 35 H pylori positive patients with gastric ulcer. 
METHODS—An endoscopic examination was carried out to diagnose ulcers and determine their clinical stage. To analyse apoptosis, a cell cycle analysis was performed using biopsy specimens. 
RESULTS—There was a significant correlation between the urease activity of the H pylori strain and the level of apoptosis induced by this bacterial strain. Moreover, in duodenal ulcer patients infected with H pylori, the patients with an active ulcer exhibited a significantly higher level of apoptosis than those with ulcers at both the healing and scarring stages. 
CONCLUSION—These findings suggest that acceleration of apoptosis in the antral mucosa caused by the urease of H pylori plays a crucial role in the development of ulcers in the duodenum. 



Keywords: apoptosis; Helicobacter pylori; urease; duodenal ulcer; gastric ulcer

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Figure 1 .

Figure 1

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Flow cytometry analysis of gastric mucosal cells. (A) The flow cytometer was gated to include single cells but to exclude any cell debris and clumps of cells according to the forward and side scatter patterns (upper panel). Single gastric mucosal cells were stained with mouse anti-epidermal growth factor receptor antibody and fluorescein isothiocyanate conjugated anti-mouse IgG antibody (lower panel, closed configuration) or fluorescein isothiocyanate conjugated anti-mouse IgG antibody only (lower panel, open configuration). (B) Representative data of the cell cycle analysis using specimens from healthy volunteers (HV) and patients with duodenal ulcer (DU) are shown, and the percentage of apoptosis cells in these specimens is also indicated. 


Figure 2 .

Figure 2

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Gastric antral biopsy samples obtained from a healthy volunteer (A) and a patient with a duodenal ulcer (B) were examined by TUNEL histochemistry. 


Figure 3 .

Figure 3

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Effect of the eradication of H pylori on the level of apoptosis. Gastric biopsy samples were taken from (A) patients with DU and (B) those with GU before the administration of antibiotics and three months after eradication therapy. The level of apoptosis in these samples was evaluated by flow cytometric analysis. A statistical analysis was performed using the paired t test. 


Figure 4 .

Figure 4

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Relation between apoptosis and the propeties of H pylori. The relation between the level of apoptosis in mucosal cells examined by flow cytometry and the bacteriological properties of H pylori including the number of bacteria in the mucosal tissue (A), the activity of the vacuolating toxin (VT) in the culture supernatant of bacteria (B), and the urease activity of the bacteria (C) were plotted. The relations between these factors were then statistically analysed by a scattergram plot. 


Figure 5 .

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Level of apoptosis at each clinical stage in ulcer disease. The level of apoptosis was examined by flow cytometry using gastric biopsy samples obtained from healthy volunteers and patients with duodenal ulcer at the active, healing, or scarring stage, and patients with gastric ulcer at the active, healing, or scarring stage. Statistical analysis was by Student's t test. 


Figure 6 .

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Histological analysis of gastric biopsy specimens. Histological features including lymphocyte infiltration (A), neutrophil infiltration (B), intestinal metaplasia (C), and epithelial erosion (D) were examined using gastric biopsy samples from healthy volunteers and patients with active, healing, and scarring duodenal ulcers, and their grades determined. Statistical analysis was by the Mann-Whitney U test. 


Figure 7 .

Figure 7

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Number of H pylori in the antral mucosa of patients with duodenal ulcer at different clinical stages. Antral biopsy samples were taken from patients with active, healing, and scarring ulcers, and the number of H pylori colonising the sample was determined. 


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