Glycoconjugates with NeuAc-NeuAc-Gal-Glc are more effective at preventing adhesion of Helicobacter pylori to gastric epithelial cells than glycoconjugates with NeuAc-Gal-Glc.
Helicobacter pylori (H. pylori) adheres to human gastric epithelial cells, eliciting various gastroduodenal diseases. Gangliosides play a critical role in bacterial adhesion to cell surfaces. The present study examined how residues of gangliosides are important for inhibition of adhesion of H. pylori to MKN-45 cells. We measured adhesion or detachment effects of gangliosides on the interaction between MKN-45 cells and H. pylori, as well as interleukin-8 production. Among the gangliosides, O-Ac-GD3, GT(1b), GD(1a), GD(1b), GT(1a), and GD3 had potent dose dependent inhibitory effects on adhesion of H. pylori to MKN-45 cells, interleukin-8 production, and vacuole formation induced by H. pylori toxin binding to Vero cells. GD3 also accelerated bacterial detachment of MKN-45 cells with adherent H. pylori in a dose dependent manner. Such results strongly suggest that the mechanism involved in the inhibition of H. pylori adhesion is mediated by the variations of the residues of the NeuAc-NeuAc-Gal-Glc chain of gangliosides. NeuAc-NeuAc-Gal-Glc exhibits a more inhibitory effect on adhesion than the NeuAc-Gal-Glc chain. Such gangioside and oligosaccrharide sequences appear to have therapeutic importance for prevention of H. pylori adhesion, as well as reduction of both inflammation and gastric mucosal injuries.
Hata
Y
Y
Department of Geriatric Medicine, Kyoto University, Kyoto, Japan.
Murakami
M
M
Okabe
S
S
D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005732:Gangliosides / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D020128:Inhibitory Concentration 50; D016209:Interleukin-8 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D013270:Stomach / Q000473:pathology; D014617:Vacuoles / Q000382:microbiology / Q000473:pathology; D014709:Vero Cells
D005732:Gangliosides; D016209:Interleukin-8; C026226:ganglioside, GD3