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Aliment Pharmacol Ther. 2000 Apr;14 Suppl 1:74-81.

A new mechanism for anti-inflammatory actions of proton pump inhibitors--inhibitory effects on neutrophil-endothelial cell interactions.

Author information

  • 1First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan. nyoshida@koto.kpu-m.ac.jp

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.

AIM:

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.

PMID:
10807407
[PubMed - indexed for MEDLINE]
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