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Cocaine, used intravenously, increases the risk of infections, but its effects on neutrophil phagocytosis have not been examined in vitro. Human neutrophils were suspended in cocaine hydrochloride 0, 1, 10, 50, 100 or 200 microg/ml in Hank's balanced salt solution to which was added a phagocytic meal of killed Saccharomyces cerevisiae stained with the pH indicator dye bromcresol purple. Yeast per phagocytosing neutrophil and the percent neutrophils phagocytosing yeast were reduced in neutrophils treated with cocaine 100 and 200 microg/ml (P < 0.05). When examined for percent of yeast phagocytosed after 10 minutes, neutrophils treated with cocaine 1-200 microg/ml demonstrated a decrease (P < 0.05). However, at 60 minutes only neutrophils treated with cocaine 50 and 100 microg/ml still showed a decrease in percent of yeast phagocytosed. Phagolysosomal acidification was impaired in neutrophils treated with 50, 100 and 200 microg/ml cocaine. Thus, cocaine inhibits neutrophil phagocytosis and phagolysosomal acidification in vitro, offering a reason for cocaine users/abusers to have impaired host defense and to be potentially at higher risk for infections.

We postulated omeprazole inhibition of the neutrophil proton pump, impairing phagocytosis and phagolysosomal acidification. Neutrophils from healthy human beings were treated with omeprazole prodrug 0.5 mM/l or acid activated omeprazole 0.5 mM/l, then incubated with killed Saccharomyces cerevisiae stained with bromcresol purple. Wet mounts were done at 10, 30 and 60 minutes. Percent neutrophils phagocytosing, percent yeast phagocytosed, and yeast per phagocytosing neutrophil were significantly decreased in acid activated omeprazole compared to controls and omeprazole prodrug. In contrast, percent acidification of intracellular yeast was significantly lower in both omeprazole prodrug and acid activated omeprazole compared to controls. Over time, control neutrophils showed an increase in percent yeast phagocytosed and yeast per phagocytosing neutrophil. When treated with acid activated omeprazole, the percent of neutrophils phagocytosing progressively decreased over time. We observed 1) omeprazole prodrug does not inhibit neutrophil phagocytosis but does inhibit phagolysosomal acidification, whereas 2) acid activated omeprazole inhibits both neutrophil phagocytosis and phagolysosome acidification. We conclude that omeprazole impairs these neutrophil functions in vitro.

We studied human neutrophils for uptake of vaccinia virus. Uptake was determined radiometrically and by electron microscopy. Vaccinia virus was labeled with 14C or 3H, incubated with neutrophils, and quantified in neutrophil pellets in a new radiometric phagocytosis assay. Better results were obtained from assays of [3H]thymidine-labeled virus; uptake increased through 1 hr and then plateaued. Phagocytosis of 3H-labeled Staphylococcus aureus was normal. Uptake of virus was serum dependent. Hexose monophosphate shunt activity was measured by two methods. No 14CO2 from [14C]1-glucose accompanied uptake of vaccinia virus, in contrast to the respiratory burst accompanying bacterial phagocytosis. Electron microscopy showed intact to slightly digested intraphagolysosomal vaccinia virus. Pock reduction assay showed a decrease in viral content due to neutrophils until 6 hr of incubation, when a modest but significant increase was observed. Thus, neutrophil uptake of vaccinia virus is distinguished from bacterial phagocytosis.