Lansoprazole inhibits oxygen-derived free radical production from neutrophils activated by Helicobacter pylori.
We studied the influence of lansoprazole on Helicobacter pylori-elicited neutrophil activation, including the oxidative burst and infiltration of gastric mucosa, and confirmed whether radiolabeled lansoprazole is actually detected in gastric neutrophils. The oxidative burst of purified human neutrophils was measured by luminol-dependent chemiluminescence (ChL). [3H]Lansoprazole uptake sites in human gastric mucosa were observed by autoradiography. The magnitude of neutrophil infiltration of gastric mucosa was assessed by tissue myeloperoxidase (MPO) content. ChL assay indicated that oxygen-derived free radical production was increased twofold by adding H. pylori water extract, which was significantly inhibited by lansoprazole (10(-4) M). Gastric biopsy samples were obtained endoscopically from patients with H. pylori-positive gastritis. Autoradiographic examination revealed that the [3H]lansoprazole binding site was present in the cytoplasmic granules of infiltrated neutrophils. Tissue MPO content was significantly decreased after treatment with lansoprazole. These data suggest that lansoprazole binds directly to neutrophils, subsequently inhibiting neutrophil accumulation and release of toxic metabolites.
Suzuki
M
M
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Nakamura
M
M
Mori
M
M
Miura
S
S
Tsuchiya
M
M
Ishii
H
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002478:Cells, Cultured; D005609:Free Radicals; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D064747:Lansoprazole; D018375:Neutrophil Activation / Q000187:drug effects*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D005609:Free Radicals; D054328:Proton Pump Inhibitors; D017382:Reactive Oxygen Species; D064747:Lansoprazole; D009853:Omeprazole