1. ¹Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
2. ²Department of Pathology, Tokyo Medical and Dental University Hospital, Tokyo, Japan
3. ³Department of Pathology, Japanese Red Cross Medical Center, Tokyo, Japan
4. ⁴Department of Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
5. ⁵Chemotherapy Department, Mitsubishi Chemical Medience, Tokyo, Japan
6. ⁶Department of Technology Assessment and Biostatistics, National Institute of Public Health, Saitama, Japan
7. ⁷Department of Stem Cell Therapy, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Correspondence: Professor Y Eishi, MD, MedScD, PhD, Department of Human Pathology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. E-mail: eishi.path@tmd.ac.jp

Received 18 February 2008; Revised 6 March 2008; Accepted 6 March 2008; Published online 12 May 2008.

Abstract

Helicobacter pylori has been considered to be non-invasive and to rarely infiltrate the gastric mucosa, even though there is an active Th1 immune response in the lamina propria of the H. pylori-infected stomach. To elucidate whether H. pylori invades the lamina propria and translocates to the gastric lymph nodes, we examined H. pylori in formalin-fixed and paraffin-embedded tissue sections of stomach and gastric lymph nodes obtained from 51 cancer patients using real-time PCR and immunohistochemistry (IHC) with a novel anti-H. pylori monoclonal antibody that recognizes lipopolysaccharides. Fresh gastric lymph nodes were used to culture for H. pylori. In 46 patients with H. pylori in the stomach, the bacterium was found in the lymph nodes from 21 patients by culture, 37 patients by PCR, and 29 patients by IHC. H. pylori captured by macrophages was found in the lamina propria of 39 patients. In the lymph nodes, the bacterium was found in many macrophages and a few interdigitating dendritic cells at the paracortical areas. H. pylori was also found in the intracellular canaliculi of parietal cells in 21 patients, but intracytoplasmic invasion into gastric epithelial cells was not identified. When compared to the commercially available anti-H. pylori antibodies, the novel antibody showed the highest sensitivity to detect H. pylori-positive macrophages, whereas no difference was found for H. pylori in the mucous layer. The H. pylori-positive macrophages in the lamina propria correlated with chronic gastritis as well as translocation of such cells to the lymph nodes. These results suggest that H. pylori-induced gastric epithelial damage allows the bacteria to invade the lamina propria and translocate to the gastric lymph nodes, which may chronically stimulate the immune system. The bacteria captured by macrophages, whether remaining alive or not, may contribute to the induction and development of H. pylori-induced chronic gastritis.