title: A new mechanism for anti-inflammatory actions of proton pump inhibitors--inhibitory effects on neutrophil-endothelial cell interactions.
abstract: BACKGROUND
  Neutrophil-endothelial cell interactions mediated by adhesion molecules may be involved in gastric mucosal inflammation associated with Helicobacter pylori or nonsteroidal anti-inflammatory drugs.
  
  
  OBJECTIVE
  To investigate the effects of proton pump inhibitors and histamine-2 receptor antagonists (HRA) on neutrophil-endothelial cell adhesive interactions induced by H. pylori water extract (HPE) or interleukin-1beta (IL-1beta).
  
  
  METHODS
  Human peripheral neutrophils and umbilical vein endothelial cells were incubated with either proton pump inhibitors (lansoprazole and omeprazole) or HRA (famotidine and ranitidine). Neutrophil surface expression of CD11b and CD18 and endothelial cell intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were assessed by flow cytometry and an enzyme immunoassay, respectively. Neutrophil adherence was defined as the ratio of exogenous neutrophils that adhered to the endothelial monolayers.
  
  
  RESULTS
  The expression of CD11b and CD18 on neutrophils and neutrophil-dependent adhesion to endothelial cells elicited by HPE were inhibited by lansoprazole and omeprazole at clinical relevant doses, and the expression of ICAM-1 and VCAM-1 on endothelial cells and endothelial-dependent neutrophil adherence induced by IL-1beta were also inhibited by lansoprazole and omeprazole at similar doses. Famotidine and ranitidine had no effect on neutrophil-endothelial cell interactions.
  
  
  CONCLUSIONS
  These results indicate that proton pump inhibitors can attenuate neutrophil adherence to endothelial cells via inhibiting the expression of adhesion molecules, suggesting that proton pump inhibitors may have anti-inflammatory activity.
authors.affiliation: First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan. nyoshida@koto.kpu-m.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Fujita
authors.forename: K
authors.initials: K
authors.lastname: Kassai
authors.forename: Y
authors.initials: Y
authors.lastname: Naito
authors.forename: M
authors.initials: M
authors.lastname: Kondo
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000494:pharmacology; D002450:Cell Communication; D018929:Cell Culture Techniques; D004727:Endothelium / Q000166:cytology* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015738:Famotidine / Q000494:pharmacology; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D064747:Lansoprazole; D009504:Neutrophils / Q000502:physiology*; D009853:Omeprazole / Q000031:analogs & derivatives / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D011899:Ranitidine / Q000494:pharmacology; D013276:Stomach Ulcer / Q000401:mortality / Q000473:pathology*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D015738:Famotidine; D011899:Ranitidine; D009853:Omeprazole