Helicobacter pylori infection recruits bone marrow-derived cells that participate in gastric preneoplasia in mice

Christine Varon, Pierre Dubus, Frederic Mazurier, Corinne Asencio, Lucie Chambonnier, Jonathan Ferrand, Alban Giese, Nathalie Senant-Dugot, Martina Carlotti, Francis Megraud

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111 Citations (Scopus)

Abstract

Studies in animal models have shown that bone marrow-derived cells (BMDC) could be involved in the formation of carcinomas of the upper gastrointestinal tract, including gastric carcinoma. Most gastric carcinomas in humans have been associated with chronic infection with Helicobacter pylori; we investigated the bacteria s potential to induce premalignant lesions in mice and studied the kinetics of BMDC settlement in the gastric epithelium. METHODS: C57BL/6J female chimeric mice with BMDCs from male donors that express green fluorescent protein were infected with human-derived and mouse-adapted strains of H pylori and followed. We assessed development of pathologic features and recruitment of BMDC to the gastric mucosa using immunohistochemistry and fluorescent in situ hybridization analyses of gastric tissue sections. RESULTS: Infection of mice with different strains of H pylori led to the development of chronic inflammation, hyperplasia, and mucinous metaplasia, and, later in life, of pseudointestinal metaplasia and dysplasia. After 1 year, gastric glands that contained green fluorescent protein-positive male cells were detected in 50 -90 of female chimeric mice infected with H pylori strains; the presence of these glands correlated with the development of pseudointestinal metaplasia. Twenty-two percent of H pylori-induced dysplastic lesions were composed of glands that contained epithelial BMDCs. CONCLUSIONS: H pylori infection leads to development of chronic inflammation, hyperplasia, metaplasia, and dysplasia, as well as the recruitment and accumulation of BMDC in the gastric epithelial mucosa. Nearly 25 of dysplastic lesions include cells that originate from the BM.
Original languageEnglish
Pages (from-to)281 - 291
Number of pages11
JournalGastroenterology
Volume142
Issue number2
DOIs
Publication statusPublished - 2012
Externally publishedYes

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