Roles of gastric mucin-type O-glycans in the pathogenesis of Helicobacter pylori infection.

Abstract

Helicobacter pylori is a Gram-negative bacterium that infects over 50% of the world's population. This organism causes various gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer. H. pylori possesses lipopolysaccharides that share structural similarity to Lewis blood group antigens in gastric mucosa. Such antigenic mimicry could result in immune tolerance against antigens of this pathogen. On the other hand, H. pylori colonizes gastric mucosa by utilizing adhesins that bind Lewis blood group antigen-related carbohydrates expressed on gastric epithelial cells. After colonization, H. pylori induces acute inflammatory responses mainly by neutrophils. This acute phase is gradually replaced by a chronic inflammatory response. In chronic gastritis, lymphocytes infiltrate the lamina propria, and such infiltration is facilitated by the interaction between L-selectin on lymphocytes and peripheral lymph node addressin (PNAd), which contains 6-sulfo sialyl Lewis X-capped O-glycans, on high endothelial venule (HEV)-like vessels. H. pylori barely colonizes gland mucous cell-derived mucin where alpha1,4-GlcNAc-capped O-glycans exist. In vitro experiments show that alpha1,4-GlcNAc-capped O-glycans function as a natural antibiotic to inhibit H. pylori growth. These findings show that distinct sets of carbohydrates expressed in the stomach are closely associated with pathogenesis and prevention of H. pylori-related diseases, providing therapeutic potentialities based on specific carbohydrate modulation.

• Authors: Motohiro Kobayashi, Heeseob Lee, Jun Nakayama, Minoru Fukuda
• Journal: Glycobiology (Glycobiology) Vol. 19 Issue 5 Pg. 453-61 (May 2009) ISSN: 1460-2423 [Electronic] England
• PMID: 19150806 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• 6'-sulfated sialyl Lewis x
• Adhesins, Bacterial
• Lewis X Antigen
• Lipopolysaccharides
• Mucin-2
• O Antigens
• Oligosaccharides
• Polysaccharides
• Sialyl Lewis X Antigen
• L-Selectin

Topics

• Adhesins, Bacterial (immunology, metabolism)
• Animals
• Chronic Disease
• Gastric Mucosa (metabolism, microbiology)
• Gastritis (metabolism, microbiology)
• Helicobacter Infections (metabolism)
• Helicobacter pylori (metabolism)
• Humans
• L-Selectin (metabolism)
• Lewis X Antigen (analogs & derivatives)
• Lipopolysaccharides (metabolism)
• Molecular Mimicry (immunology)
• Mucin-2 (metabolism)
• Neutrophils (immunology)
• O Antigens (immunology, metabolism)
• Oligosaccharides (metabolism)
• Peptic Ulcer (metabolism, microbiology)
• Polysaccharides (metabolism)
• Sialyl Lewis X Antigen (analogs & derivatives)
• Stomach Neoplasms (metabolism, microbiology)