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Role of phosphate, pyrophosphate, adenine nucleotides and sulfate in activating production of the superoxide radical by macrophages, and in formation of rat paw edema

  • Immunosuppression and Inflammation
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Abstract

The presence of anions of phosphate (Pi), pyrophosphate (PPi), adenine nucleotides and sulfate greatly enhanced the production of superoxide radical (·O 2 ) by isolated guinea-pig macrophages. These anions, however, failed to enhance the production of ·O 2 by the xanthine oxidase system, suggesting that they serve only as activators of ·O 2 generating enzyme(s) located on the macrophage cell membrane. Many other common anions were ineffective in the macrophage system. In the presence of concentrations of Pi, PPi, adenine-5′-triphosphate (ATP) reported to be in the synovial fluid, ·O 2 was produced efficiently and was inhibited by diclofenac sodium.

These anions induced rat paw edema, maintained the swelling at least up to 6 h. The edema was suppressed partially by repeated injection of superoxide dismutase (SOD). High doses of sodium chloride and nitrate failed to maintain the swelling.

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References

  1. Y. Ōyanagui,Inhibitions of Superoxide Anion Productions in Macrophages by Anti-Inflammatory Drugs, Biochem. Pharmac.25, 1473–1480 (1976).

    Google Scholar 

  2. Y. Ōyanagui,Participation of Superoxide Anions at Prostaglandin Phase of Carrageenan Foot-Oedema, Biochem. Pharmac.25, 1465–1472 (1976).

    Google Scholar 

  3. R.G.G. Russell, S. Bisaz, H. Fleisch, H.L.F. Currey, H.M. Rubinstein, A.A. Dietz, I. Boussina, A. Micheli andG. Fallet,Inorganic Pyrophosphate in Plasma, Urine, and Synovial Fluid of Patients with Pyrophosphate Arthropathy (Chondrocalcinosis or Pseudogout). LancetII, 899–902 (1970).

    Google Scholar 

  4. D.J. McCarty andP.F. Pepe,Erythrocyte Neutral Inorganic Pyrophosphatase in Pseudogout, J. Lab. Clin. Med.79, (2), 277–284 (1972).

    PubMed  Google Scholar 

  5. D.J. McCarty, D.C. Silcox, F. Coe, S. Jacobelli, E. Reiss, H. Genant andM. Ellman,Diseases Associated with Calcium Pyrophosphate Dihydrate Crystal Deposition-A Controlled Study, Am. J. Med.56, 704–714 (1974).

    PubMed  Google Scholar 

  6. D.C. Silcox andD.J. McCarty,Elevated Inorganic Pyrophosphate Concentrations in Synovial Fluids in Osteoarthritis and Pseudogout, J. Lab. Clin. Med.83, 518–531 (1974).

    PubMed  Google Scholar 

  7. K. Tomita, A. Ichikawa andH. Hayashi Effects of Cyclic 3′,5′-Adenosine Monophosphate on Inflammations Induced by Inorganic Pyrophosphate, ATP and Other Phlogistins, Japan J. Pharmacol. Suppl. 8 (1972).

  8. D.A. Willoughby, C.J. Dunn, S. Yamamoto, F. Capasso, D.A. Deporter andJ.P. Giroud,Calcium Pyrophosphate-Induced Pleurisy in Rats: A New Model of Acute Inflammation, Agents and Actions5 (1), 35–38 (1975).

    PubMed  Google Scholar 

  9. A. Yoshimoto, H. Ito andK. Tomita,Cofactor Requirements of the Enzyme Synthesizing Prostaglandin in Bovine Seminal Vessicles, J. Biochem. (Tokyo)68, 487–499 (1970).

    Google Scholar 

  10. J.T. Curnutte andB.M. Babior,Effects of Anaerobiosis and Inhibitors on ·O 2 Production of Human Granulocytes, Blood45 (6), 851–861 (1975).

    PubMed  Google Scholar 

  11. M. Camerlain, D.J. McCarty, D.C. Silcox andA. Jung,Inorganic Pyrophosphate Pool Size and Turnover Rate in Arthritic Joints, J. clin. Invest.55, 1373–1381 (1975).

    PubMed  Google Scholar 

  12. J. Roger undD.A. Kalbhen,Der Adenosintriphosphat-Gehhalt des Knorpels unter dem Einfluss verschiedener Antirheumatica in vitro, Arzneim. Forsch.18, 1512–1516 (1968).

    Google Scholar 

  13. R.T. Briggs, D.B. Drath, M.J. Karnovsky andM.L. Karnovsky,Surface Localization of NADH Oxidase in Polymorphonuclear Leycocytes, J. Cell. Biol.63, 36a (1974).

    Google Scholar 

  14. K. Takanaka andP.J. O'Brien,Mechanism of H 2 O 2 Formation by Leukocytes — Evidence for a Plasma Membrane Location, Arch. Biochem. Biophys.169, 428–435 (1975).

    PubMed  Google Scholar 

  15. R.L. Tse andP. Phelps,Polymorphonuclear Leukocyte Motility in vivo. V. Release of Chemotactic Activity Following Phagocytosis of Calcium Pyrophosphate Crystals. Diamond Dust and Urate Crystals, J. Lab. Clin. Med.76 (3), 403–415 (1970).

    PubMed  Google Scholar 

  16. D.S. Howell, O. Muniz, J.C. Pita andJ.E. Enis,Extrusion of Pyrophosphate into Extracellular Media by Osteoarthritic Cartilage Incubates, J. clin. Invest.56, 1473–1480 (1975).

    PubMed  Google Scholar 

  17. R.M. Bennett, J.R. Lehr andD.J. McCarty,Factors Affecting the Solubility of Calcium Pyrophosphate Dihydrate Crystals, J. clin. Invest.56, 1571–1579 (1975).

    PubMed  Google Scholar 

  18. P. Needlemann, M.S. Minks andR. Douglas Jr.,Stimulation of Prostaglandin Biosynthesis by Adenine Nucleotides — Profile of Prostaglandin Release by Perfused Organs, Circulation Res.34, 455–460 (1974).

    PubMed  Google Scholar 

  19. M. Höök, Å. Wasteson andA. Oldberg,A Heparin Sulfate-Degrading Endoglycosidase from Rat Liver Tissue, Bioch. Bioph. Res. Commun.67 (4), 1422–1428 (1975).

    Google Scholar 

  20. P. Ghosh, R.W. Stephens andT.K.F. Taylor,The Inhibition of Synovial Fluid Polysaccharides by Gold Sodium Thiomalate, Med. J. Aust.1 (10), 317 (1975).

    Google Scholar 

  21. J.M. McCord,Free Radicals and Inflammation: Protection of Synovial Fluid by Superoxide Dismutase, Science185, 529–531 (1974).

    PubMed  Google Scholar 

  22. L.S. Cusbing, W.E. Decker, F.K. Santos andT.L. Schulte,Orgotein Therapy for Inflammation in Horses, Modern Vet. Practice54 (7), 17–21 (1973).

    Google Scholar 

  23. K. Lund-Olesen andK.B. Menander,Orgotein: A New Anti-Inflammatory Metalloprotein Drug: Preliminary Evaluation of Clinical Efficacy and Safety in Degenerative Joint Disease, Current Therapeutic Res.16 (7), 706–717 (1974).

    Google Scholar 

  24. R.J. Flower andG.J. Blackwell The Importance of Phospholipase-A 2 in Prostaglandin Biosynthesis, Biochem. Pharmac.25, 285–291 (1976).

    Google Scholar 

  25. K.-L. Fong, P.B. McCay andJ.L. Poyer,Evidence that Peroxidation of Lysosomal Membranes is Initiated by Hydroxyl Free Radicals Produced during Flavine Enzyme Activity, J. biol. Chem.248 (22), 7792–7797 (1973).

    PubMed  Google Scholar 

  26. C. Malmsten, M. Hamberg, J. Svenson andB. Samuelsson,Physiological Role of an Endoperoxide in Human Platelets: Hemostatic Defect Due to Platelet Cyclo-Oxygenase Deficiency, Proc. Nat. Acad. Sci. USA72(4), 1446–1450 (1975).

    PubMed  Google Scholar 

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Ōyanagui, Y. Role of phosphate, pyrophosphate, adenine nucleotides and sulfate in activating production of the superoxide radical by macrophages, and in formation of rat paw edema. Agents and Actions 7, 125–132 (1977). https://doi.org/10.1007/BF01964910

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