Induction of peripheral lymph node addressin in human gastric mucosa infected by Helicobacter pylori.

Abstract

Helicobacter pylori infects over half the world's population and is a leading cause of peptic ulcer and gastric cancer. H. pylori infection results in chronic inflammation of the gastric mucosa, and progression of chronic inflammation leads to glandular atrophy and intestinal metaplasia. However, how this chronic inflammation is induced or maintained is not well known. Here, we show that chronic inflammation caused by H. pylori infection is highly correlated with de novo synthesis of peripheral lymph node addressin (PNAd) presented on high-endothelial venule (HEV)-like vessels. The number of HEV-like vessels dramatically increases as chronic inflammation progresses. We found that the PNAd is bound by L-selectin.IgM chimeric protein, and decorated by NCC-ST-439 antibody, which is suggested to recognize both nonsulfated and 6-sulfated sialyl Lewis X on core 2 branched O-glycans, and MECA-79 antibody, which reacts with 6-sulfo N-acetyllactosamine on extended core 1 O-glycans. These results indicate that PNAd on HEV-like vessels present in the gastric mucosa subsequent to H. pylori infection is similar to those on HEVs present in the secondary lymphoid organs, which are essential for lymphocyte circulation. Moreover, eradication of H. pylori is associated with the disappearance of HEV-like vessels in the gastric mucosa. By contrast, very few PNAd were found in the gastric mucosa of patients with chemical gastritis caused by nonsteroidal antiinflammatory drugs. These results strongly suggest that PNAd in HEV-like vessels plays a critical role in lymphocyte recruitment during chronic inflammation induced by H. pylori infection.

• Authors: Motohiro Kobayashi, Junya Mitoma, Naoshi Nakamura, Tsutomu Katsuyama, Jun Nakayama, Minoru Fukuda
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 101 Issue 51 Pg. 17807-12 (Dec 21 2004) ISSN: 0027-8424 [Print] United States
• PMID: 15591109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antigens, Surface
• L-selectin counter-receptors
• Membrane Proteins

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects)
• Antigens, Surface (metabolism)
• CHO Cells
• Cricetinae
• Gastric Mucosa (blood supply, drug effects, metabolism, microbiology)
• Gastritis (chemically induced, pathology)
• Helicobacter Infections (complications, metabolism, microbiology, pathology)
• Helicobacter pylori (physiology)
• Humans
• Inflammation (chemically induced, complications, microbiology, pathology)
• Lymph Nodes (blood supply, metabolism, microbiology, pathology)
• Membrane Proteins
• Mice