SS1 Helicobacter pylori disrupts the paracellular barrier of the gastric mucosa and leads to neutrophilic gastritis in mice.
Helicobacter pylori induces severe neutrophilic infiltration in the lamina propria of the stomach, which leads to gastritis in humans. The possible involvement of a paracellular route for bacterial nutrients and etiologic agents that may play an important role in colonization of the bacteria and cause gastritis has been suggested. To study the functions of the paracellular barrier of gastric surface epithelium, SS1, a strain of H. pylori adapted to the murine stomach, was inoculated into the stomachs of C57BL/6 mice. At 4 months after inoculation, SS1 had achieved a high level of colonization (10(6)-10(7) colony-forming units/g tissue) associated with neutrophilic infiltration in the lamina propria of the junctional zone. Disruption of the paracellular barrier was observed in the SS1-infected stomachs, as revealed by the invasion of a lanthanum tracer into the paracellular space of the surface epithelium. Only 2% of junctions were permeable in control stomachs, whereas 72% of the paracellular barrier was disrupted in the SS1-infected gastric epithelia. Furthermore, distribution of tight junction-related molecules such as 7H6 antigen, occludin, and cortical actin was affected in the surface epithelium by SS1 infection. The linear expression pattern of occludin was disrupted and became irregular or punctuated. The 7H6 antigen accumulated as aggregates in the apical portion of the surface epithelium and cortical actin became irregular and punctuated. Taken together, these results indicate that infection by SS1 directly or indirectly caused an increase in paracellular permeability and altered the localization of tight junction-related molecules of the gastric surface epithelium. This observation suggests that the paracellular pathway may play a significant role in establishing H. pylori-induced gastritis in the clinical setting.
Suzuki
Ken-ichi
K
Department of Pathology, Sapporo Medical University School of Medicine, S1W17, Chuo-ku, Sapporo, 060-8556, Japan.
Kokai
Yasuo
Y
Sawada
Norimasa
N
Takakuwa
Reiko
R
Kuwahara
Kazuhide
K
Isogai
Emiko
E
Isogai
Hiroshi
H
Mori
Michio
M
D000199:Actins / Q000378:metabolism; D000818:Animals; D002463:Cell Membrane Permeability; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D016480:Helicobacter pylori / Q000472:pathogenicity / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D019108:Tight Junctions
D000199:Actins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; C089734:antigen 7H6