Helicobacter pylori attaches to NeuAc alpha 2,3Gal beta 1,4 glycoconjugates produced in the stomach of transgenic mice lacking parietal cells.
Helicobacter pylori infection of the human stomach is associated with altered acid secretion, loss of acid-producing parietal cells, and, in some hosts, adenocarcinoma. We have used a transgenic mouse model to study the effects of parietal cell ablation on H. pylori pathogenesis. Ablation results in amplification of the presumptive gastric epithelial stem cell and its immediate committed daughters. The amplified cells produce sialylated oncofetal carbohydrate antigens that function as receptors for H. pylori adhesins. Attachment results in enhanced cellular and humoral immune responses. NeuAc alpha 2,3Gal beta 1,4 glycoconjugates may not only facilitate persistent H. pylori infection in a changing gastric ecosystem, but by promoting interactions with lineage progenitors and/or initiated cells contribute to tumorigenesis in patients with chronic atrophic gastritis.
Syder
A J
AJ
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Guruge
J L
JL
Li
Q
Q
Hu
Y
Y
Oleksiewicz
C M
CM
Lorenz
R G
RG
Karam
S M
SM
Falk
P G
PG
Gordon
J I
JI
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D001422:Bacterial Adhesion; D002455:Cell Division; D019070:Cell Lineage; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure; D006001:Glycoconjugates / Q000378:metabolism*; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000254:growth & development / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D037102:Lectins / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D010295:Parietal Cells, Gastric / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure
D000951:Antigens, Neoplasm; D006001:Glycoconjugates; D037102:Lectins; C031192:oncofetal antigens; D019158:N-Acetylneuraminic Acid