Gastroenterology

Gastroenterology

Volume 118, Issue 1, January 2000, Pages 48-59
Gastroenterology

Alimentary Tract
Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in Mongolian gerbils,☆☆

https://doi.org/10.1016/S0016-5085(00)70413-6Get rights and content

Abstract

Background & Aims: Human colonization with Helicobacter pylori increases the risk for distal gastric adenocarcinoma, possibly by altering gastric epithelial cell cycle events and/or gastrin secretion. This study aimed to determine whether H. pylori virulence–related characteristics affect apoptosis, proliferation, and gastrin levels in a rodent model of gastric adenocarcinoma. Methods: Mongolian gerbils were challenged with H. pylori wild-type or isogenic cagA and vacA mutants, and apoptotic and proliferating cells were identified by terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling and proliferating cell nuclear antigen immunohistochemistry, respectively. Serum gastrin levels were determined by radioimmunoassay. Results: Gastric epithelial cell turnover was no different after infection with the wild-type, cagA, or vacA strains. H. pylori infection significantly increased antral apoptosis 2-4 weeks after challenge, before apoptotic indices decreased to baseline. In contrast, antral proliferation rates were significantly higher 16-20 weeks after inoculation, but then decreased by 40 weeks. Antral proliferation was significantly related to serum gastrin levels, whereas antral apoptosis was inversely related to acute inflammation and lymphoid follicles. Conclusions: In H. pylori–infected gerbils, enhanced antral apoptosis is an early and transient cell cycle event. Epithelial cell proliferation peaks later and is significantly related to increased gastrin levels, suggesting that epithelial cell growth in H. pylori–colonized mucosa may be mediated by gastrin-dependent mechanisms.

GASTROENTEROLOGY 2000;118:48-59

Section snippets

Animals and housing and H. pylori challenge

Outbred Mongolian gerbils of 30-50 g body weight, corresponding to an age of approximately 4-8 weeks, were purchased either from Harlan Sprague Dawley, Inc. (Indianapolis, IN) (Hsd:MON) or Charles River Laboratories (Wilmington, MA) (Crl:[MON]BR[outbred]), exactly as described previously.24 All experiments and procedures carried out on the animals were approved by the Institutional Animal Care Committee of Vanderbilt University. The mouse-passaged cagA+, vacA s1a toxigenic strain CPY340124 was

Colonization efficiency of wild-type and isogenic mutant H. pylori strains

The population of animals examined in the current study has been described previously by Wirth et al.24 In total, 120 gerbils had been challenged either with H. pylori strain G1.1 WT (n = 60), G1.1 C (n = 23), G1.1 V (n = 17), or brucella broth alone (n = 20).24 Because indices of cell turnover and gastrin levels in uninfected gerbils did not vary by age, the control animals were analyzed together as a single group. Of the 100 gerbils challenged with H. pylori, 93 (57 WT, 22 C, 14 V) were

Discussion

Apoptosis is a normal component of epithelial cell turnover in the gastrointestinal tract, and most studies show that persons colonized with H. pylori have increased rates of gastric mucosal proliferation and apoptosis compared with uninfected persons.11, 12, 13, 14, 29 However, within clinical populations, there is substantial overlap in these measures of gastric epithelial cell growth and death. H. pylori strain–specific characteristics may contribute to this heterogeneity; persons carrying

Acknowledgements

The authors thank Uma Krishna and Annuapama Voodarla for excellent technical assistance.

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    Address requests for reprints to: Richard M. Peek, Jr., M.D., Division of Gastroenterology, Vanderbilt University School of Medicine, C-2104 Medical Center North, Nashville, Tennessee 37232-2279. e-mail: [email protected]; fax: (615) 343-6229.

    ☆☆

    Supported in part by the National Institutes of Health grants KO8 DK02381-01A3, R29 CA77955, and R01 DK50837 and the Medical Research Service of the Department of Veterans Affairs.

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