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Type: Artigo de periódico
Title: The inhibitory effects of H(+)K(+)ATPase inhibitors on human neutrophils in vitro: Restoration by a K+ ionophore
Author: de Oliveira, RM
Antunes, E
Pedrazzoli, J
Gambero, A
Abstract: Objective: This study investigated the ability of proton pump inhibitors (PPI), such as omeprazole and pantoprazole, to inhibit neutrophil migration, calcium mobilization and the mechanisms involved in this inhibition. Methods: Neutrophils were incubated with different concentrations of omeprazole and pantoprazole for 30 min and stimulated to migrate with fMLP and IL-8. Treatment toxicity was assessed by MTT assay. The intracellular calcium levels were analyzed in neutrophils pre-treated with omeprazole and pre-loaded with FURA-2AM, when stimulated with fMLP. The activity of p38 MAP Kinase was evaluated by Western blot after treatment with omeprazole. Results: Omeprazole is able to inhibit neutrophil chemotaxis to fMLP and IL-8. Pantoprazole demonstrated the same ability. This inhibitory effect was not due to a toxic effect of the proton pump inhibitors. Inhibition of v-ATPase by bafilomycin did not modify the ability of fMLP or IL-8 to induce neutrophil migration. Omeprazole was also able to decrease intracellular calcium availability. The addition of a potassium ionophore, nigericin, restored the migratory ability, as well as the intracellular calcium levels. The activity of p38 MAP Kinase was decreased in neutrophils pretreated with omeprazole. Conclusion: Proton pump inhibitors promote inhibition of H(+)K(+)ATPase in neutrophils, resulting in cationic flow disturbances through the cellular membrane that, consequently, inhibit migratory and intracellular events such as calcium influx and p38 MAP Kinase activation.
Subject: fMLP
p38 MAP kinase
Country: Suíça
Editor: Birkhauser Verlag Ag
Rights: fechado
Identifier DOI: 10.1007/s00011-006-6127-6
Date Issue: 2007
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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