Omeprazole inhibits phagocytosis and acidification of phagolysosomes of normal human neutrophils in vitro

We postulated omeprazole inhibition of the neutrophil proton pump, impairin g phagocytosis and phagolysosomal acidification. Neutrophils from healthy h uman beings were treated with omeprazole prodrug 0.5 mM/1 or acid activated omeprazole 0.5 mM/1, then incubated with killed Saccharomyces cerevisiae s tained with bromcresol purple. Wet mounts were done at 10, 30 and 60 minute s. Percent neutrophils phagocytosing, percent yeast phagocytosed, and yeast per phagocytosing neutrophil were significantly decreased in acid activate d omeprazole compared to controls and omeprazole prodrug. In contrast, perc ent acidification of intracellular yeast was significantly lower in both om eprazole prodrug and acid activated omeprazole compared to controls. Over t ime, control neutrophils showed an increase in percent yeast phagocytosed a nd yeast per phagocytosing neutrophil. When treated with acid activated ome prazole, the percent of neutrophils phagocytosing progressively decreased o ver time. We observed 1) omeprazole prodrug does not inhibit neutrophil pha gocytosis but does inhibit phagolysosomal acidification, whereas 2) acid ac tivated omeprazole inhibits both neutrophil phagocytosis and phagolysosome acidification. We conclude that omeprazole impairs these neutrophil functio ns in vitro.