Functional role of metaplastic paneth cell defensins in Helicobacter pylori-infected stomach.
OBJECTIVE
Chronic gastritis is caused by Helicobacter pylori infection, and gastritis is classified as inflammation, atrophy, and intestinal metaplasia. Detailed pathologic studies have shown that H. pylori settles on the surface of gastric mucosa, and that it is eliminated from metaplastic mucosa. However, its mechanism of natural protection is not well known.


METHODS
Antimicrobial human enteric defensin expression was determined in the RNA and protein levels. Recombinant enteric defensins were produced with a bacterial expression system and their anti-H. pylori activities were assessed by bactericidal assay.


RESULTS
Human enteric defensin (HD)-5 and HD-6 were detected in Paneth cells, which are observed in the gastric metaplastic mucosa as well as small intestinal epithelia. HD-5 protein was coexpressed with trypsin, which is considered to be an activating enzyme of HD-5. Less H. pylori was observed in the intestinal metaplasia with HD-5 expressing Paneth cells. The recombinant defensins showed killing activity against H. pylori at a low concentration in vitro.


CONCLUSIONS
The human defensins that are expressed in the metaplastic Paneth cells eliminate H. pylori. Metaplastic change may be a purposive development of the human stomach.
Tanabe
Hiroki
H
Department of Internal Medicine, Division of Gastroenterology and Haematology/Oncology, Asahikawa Medical College, Asahikawa, Hokkaido, Japan. tant@asahikawa-med.ac.jp
Sato
Tomonobu
T
Watari
Jiro
J
Maemoto
Atsuo
A
Fujiya
Mikihiro
M
Fijiya
Mikihiko
M
Kono
Toru
T
Ashida
Toshifumi
T
Ayabe
Tokiyoshi
T
Kohgo
Yutaka
Y
D015153:Blotting, Western; D023082:Defensins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology; D016481:Helicobacter Infections / Q000382:microbiology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008679:Metaplasia / Q000378:metabolism* / Q000382:microbiology; D019879:Paneth Cells / Q000378:metabolism* / Q000382:microbiology; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000166:cytology / Q000382:microbiology*
D023082:Defensins; D011994:Recombinant Proteins