Long-standing gastric mucosal barrier dysfunction in Helicobacter pylori-induced gastritis in mongolian gerbils.
OBJECTIVE
Helicobacter pylori infection causes chronic gastritis and leads to peptic ulcer and gastric adenocarcinoma. An impaired gastric mucosal barrier could be involved in these processes. Our aim was to investigate gastric barrier function in H. pylori-induced gastritis.


METHODS
Stripped gastric mucosal tissues of H. pylori-infected Mongolian gerbils (4 weeks and 70 weeks after inoculation, respectively) and controls were mounted in Ussing chambers. (51)Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP, protein antigen) were used to assess mucosal barrier function. The electrophysiological parameters of the mucosa (transepithelial potential, short circuit current, and transepithelial resistance) were monitored as measurements of barrier integrity and viability. Tissue histology was performed to assess inflammation.


RESULTS
In the antrum, both short-term gastritis [4.68 (3.88-5.74) x 10(-6) vs. control 2.86 (2.34-3.77) x 10(-6) cm/s, p <.001] and gastritis of long-standing [5.72 (3.88-10.94) x 10(-6) cm/s, p <.001 vs. control] showed increased permeability to (51)Cr-EDTA. In long-standing antral gastritis there was also an increased HRP flux [9.01 (2.98-45.02) vs. control 0.52 (0.06-1.20) pmol/h/cm(2), p <.001]. In the corpus, permeability to (51)Cr-EDTA was increased only in long-standing gastritis [4.63 (3.64-7.45) x 10(-6) vs. control 2.86 (2.12-3.98) x 10(-6) cm/s, p <.01]. Gastric mucosal permeability to (51)Cr-EDTA was correlated to histological inflammation and inflammatory activity. The levels of serum anti-H. pylori immunoglobulin G were positively correlated to HRP flux and (51)Cr-EDTA permeation.


CONCLUSIONS
Helicobacter pylori-induced gastritis in Mongolian gerbils was associated with a long-standing gastric mucosal barrier dysfunction. The barrier defect extended from the antrum into the corpus over time. This impaired barrier function may contribute to perpetuation of chronic inflammation and may be involved in H. pylori-associated carcinogenesis.
Sun
Yi-Qian
YQ
Division of Surgery, Department of Biomedicine and Surgery, Faculty of Health Sciences, University of Linköping, Sweden. yisun@ibk.liu.se
Söderholm
Johan D
JD
Petersson
Fredrik
F
Borch
Kurt
K
D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D002860:Chromium Radioisotopes / Q000378:metabolism; D004594:Electrophysiology; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006735:Horseradish Peroxidase / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D008854:Microscopy, Electron
D002860:Chromium Radioisotopes; D007074:Immunoglobulin G; D006735:Horseradish Peroxidase