Effect of Phenylbutazone on Phagocytosis and Intracellular Killing by Guinea Pig Polymorphonuclear Leukocytes1

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RESUMO

The anti-inflammatory drug phenylbutazone has been found to inhibit both engulfment and intracellular killing of E. coli by guinea pig peritoneal polymorphonuclear (PMN) leukocytes. The bactericidal activity of leukocytic homogenates was also inhibited by the drug. Addition of the drug at various time intervals to a phagocytic reacting system caused an almost immediate cessation of bactericidal activity. Metabolic studies showed that the drug sharply curtailed glucose-l-14C and 14C-formate oxidation of both resting and phagocytizing PMN leukocytes. These data indicated an effect upon the hexose monophosphate shunt and H2O2 formation. Further investigation showed that the sites of inhibition were on glucose-6-phosphate and 6-phosphogluconate dehydrogenase. These inhibitions resulted in decreased H2O2 production. It is suggested that H2O2 activates lysosomes and subsequently complexes with the lysosomal enzyme, myeloperoxidase. This complex is a potent bactericidal agent in the phagocyte.

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