Skip to main content
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1968 Dec;96(6):1982–1990. doi: 10.1128/jb.96.6.1982-1990.1968

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

Robert R Strauss 1,2, Benoy B Paul 1,2, Anthony J Sbarra 1,2
PMCID: PMC252546  PMID: 4881700

Abstract

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.

Full text

PDF
1982

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. HIRSCH J. G. Phagocytin: a bactericidal substance from polymorphonuclear leucocytes. J Exp Med. 1956 May 1;103(5):589–611. doi: 10.1084/jem.103.5.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Holmes B., Page A. R., Good R. A. Studies of the metabolic activity of leukocytes from patients with a genetic abnormality of phagocytic function. J Clin Invest. 1967 Sep;46(9):1422–1432. doi: 10.1172/JCI105634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. IYER G. Y., QUESTEL J. H. NADPH and NADH oxidation by guinea pig polymorphonuclear leucocytes. Can J Biochem Physiol. 1963 Feb;41:427–434. [PubMed] [Google Scholar]
  4. Klebanoff S. J. Iodination of bacteria: a bactericidal mechanism. J Exp Med. 1967 Dec 1;126(6):1063–1078. doi: 10.1084/jem.126.6.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Klebanoff S. J. Myeloperoxidase-halide-hydrogen peroxide antibacterial system. J Bacteriol. 1968 Jun;95(6):2131–2138. doi: 10.1128/jb.95.6.2131-2138.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Mayer S. E., Mayfield A. C., Haas J. A. Heart muscle hexokinase: subcellular distribution and inhibition by glucose 6-phosphate. Mol Pharmacol. 1966 Sep;2(5):393–405. [PubMed] [Google Scholar]
  7. McRipley R. J., Sbarra A. J. Role of the phagocyte in host-parasite interactions. XI. Relationship between stimulated oxidative metabolism and hydrogen peroxide formation, and intracellular killing. J Bacteriol. 1967 Nov;94(5):1417–1424. doi: 10.1128/jb.94.5.1417-1424.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McRipley R. J., Sbarra A. J. Role of the phagocyte in host-parasite interactions. XII. Hydrogen peroxide-myeloperoxidase bactericidal system in the phagocyte. J Bacteriol. 1967 Nov;94(5):1425–1430. doi: 10.1128/jb.94.5.1425-1430.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Nake T., Nakano M., Saito K. Metabolic study of intracellular killing of bacteria by mouse macrophages. Jpn J Microbiol. 1967 Sep;11(3):189–201. doi: 10.1111/j.1348-0421.1967.tb00336.x. [DOI] [PubMed] [Google Scholar]
  10. Paul B., Sbarra A. J. The role of the phagocyte in host-parasite interactions. 13. The direct quantitative estimation of H2O2 in phagocytizing cells. Biochim Biophys Acta. 1968 Feb 1;156(1):168–178. doi: 10.1016/0304-4165(68)90116-5. [DOI] [PubMed] [Google Scholar]
  11. ROSSI F., ZATTI M. CHANGES IN THE METABOLIC PATTERN OF POLYMORPHO-NUCLEAR LEUCOCYTES DURING PHAGOCYTOSIS. Br J Exp Pathol. 1964 Oct;45:548–559. [PMC free article] [PubMed] [Google Scholar]
  12. SBARRA A. J., KARNOVSKY M. L. The biochemical basis of phagocytosis. I. Metabolic changes during the ingestion of particles by polymorphonuclear leukocytes. J Biol Chem. 1959 Jun;234(6):1355–1362. [PubMed] [Google Scholar]
  13. SCHULTZ J., SHMUKLER H. W. MYELOPEROXIDASE OF THE LEUCOCYTE OF NORMAL HUMAN BLOOD. II. ISOLATION, SPECTROPHOTOMETRY, AND AMINO ACID ANALYSIS. Biochemistry. 1964 Sep;3:1234–1238. doi: 10.1021/bi00897a009. [DOI] [PubMed] [Google Scholar]
  14. Selvaraj R. J., Sbarra A. J. Phagocytosis inhibition and reversal. II. Possible role of pyruvate as an alternative source of energy for particle uptake by guinea-pig leukocytes. Biochim Biophys Acta. 1966 Sep 26;127(1):159–171. doi: 10.1016/0304-4165(66)90486-7. [DOI] [PubMed] [Google Scholar]
  15. Selvaraj R. J., Sbarra A. J. Relationship of glycolytic and oxidative metabolism to particle entry and destruction in phagocytosing cells. Nature. 1966 Sep 17;211(5055):1272–1276. doi: 10.1038/2111272a0. [DOI] [PubMed] [Google Scholar]
  16. Skarnes R. C. Leukin, a bactericidal agent from rabbit polymorphonuclear leucocytes. Nature. 1967 Nov 25;216(5117):806–808. doi: 10.1038/216806a0. [DOI] [PubMed] [Google Scholar]
  17. WHITEHOUSE M. W. UNCOUPLING OF OXIDATIVE PHOSPHORYLATION BY SOME ARYLACETIC ACIDS (ANTI-INFLAMMATORY OR HYPERCHOLESTEROLEMIC DRUGS). Nature. 1964 Feb 8;201:629–630. doi: 10.1038/201629a0. [DOI] [PubMed] [Google Scholar]
  18. Weissmann G. Lysosomes and joint disease. Arthritis Rheum. 1966 Dec;9(6):834–840. doi: 10.1002/art.1780090611. [DOI] [PubMed] [Google Scholar]
  19. Weissmann G. The role of lysosomes in inflammation and disease. Annu Rev Med. 1967;18:97–112. doi: 10.1146/annurev.me.18.020167.000525. [DOI] [PubMed] [Google Scholar]
  20. ZEYA H. I., SPITZNAGEL J. K. ANTIBACTERIAL AND ENZYMIC BASIC PROTEINS FROM LEUKOCYTE LYSOSOMES: SEPARATION AND IDENTIFICATION. Science. 1963 Nov 22;142(3595):1085–1087. doi: 10.1126/science.142.3595.1085. [DOI] [PubMed] [Google Scholar]
  21. Zeya H. I., Spitznagel J. K. Cationic proteins of polymorphonuclear leukocyte lysosomes. II. Composition, properties, and mechanism of antibacterial action. J Bacteriol. 1966 Feb;91(2):755–762. doi: 10.1128/jb.91.2.755-762.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES