Thromb Haemost 1981; 46(03): 584-589
DOI: 10.1055/s-0038-1653423
Original Article
Schattauer GmbH Stuttgart

Arachidonic Acid-Induced Chemiluminescence of Human Platelets: Contribution of the Prostaglandin and Lipoxygenase Pathways

P Wörner
The Dept. of Immunology and Serology, Institute for Hygiene and Med. Microbiology, Klinikum Mannheim, Universität Heidelberg, Mannheim, West Germany
› Author Affiliations
Further Information

Publication History

Received 09 April 1981

Accepted 15 June 1981

Publication Date:
05 July 2018 (online)

Summary

Two signals of chemiluminescence are observed when platelets are exposed to arachidonic acid in the presence of luminol. Three groups of agents interfere with these luminescence responses. Inhibitors of cyclooxygenase, known to augment the turnover of arachidonic acid by lipoxygenase, inhibit the first and enhance the second signal of luminescence.

Sodium azide, diamide, NEM, and the endoperoxide analogues U 44069 and U 46619 interfere with the second luminescence signal but not with the first one nor with the generation of MDA. These agents may represent selective inhibitors of the lipoxygenase pathway.

Phenidone, nordihydroguaiaretic acid, quercetin, silybin, phenylthiazolyl-thiourea, and aminotriazole inhibit both luminescence signals promoted by arachidonic acid.

Measurement of luminescence may provide a tool to follow the time course of arachidonic-acid turnover by prostaglandin synthetase and lipoxygenase in whole cells.

 
  • References

  • 1 Allen RC, Stjernholm RL, Steele RH. Evidence for the generation of an electronic excitation state(s) in human polymorphonuclear leukocytes and its participation in bactericidal activity. Biochem Biophys Res Commun 1972; 47: 679-684
  • 2 Cheson BD, Christensen RL, Sperling GR, Kohler BE, Babior BM. The origin of chemiluminescence of phagocytosing granulocytes. J Clin Invest 1976; 58: 789-796
  • 3 Sagone AL, Mendelson DS, Metz EN. The effect of sodium azide on the chemiluminescence of granulocytes - evidence for the generation of multiple oxygen radicals. J Lab Clin Med 1977; 89: 1333-1340
  • 4 Weidemann MJ, Peskar BA, Wrogemann K, Rietschel ET, Staudinger H, Fischer H. Prostaglandin and thromboxane synthesis in a pure macrophage population and the inhibition by E-type prostaglandins, of chemiluminescence. FEBS Lett 1978; 89: 136-140
  • 5 Miles PR, Castranova V, Lee P. Reactive forms of oxygen and chemiluminescence in phagocytosing rabbit alveolar macrophages. Am J Physiol 1978; 253: C103-C108
  • 6 Tauber AI, Gabing TG, Babior BM. Evidence for production of oxidizing radicals by the particulate O2-forming system from human neutrophils. Blood 1979; 53: 666-676
  • 7 Nelson RD, Herron MJ, Schmidtke JR, Simmons RL. Chemiluminescence response of human leukocytes: influence of medium components on light production. Infection Immun 1977; 17: 513-520
  • 8 White EH, Zafiriou O, Kägi HH, Hill JH M. Chemiluminescence of luminol: the chemical reaction. J Am Chem Soc 1964; 86: 940-941
  • 9 Krinsky NI, Scoon KL, Handin JC, Levine PH. Source of hydrogen peroxide and of chemiluminescence observed in activated human platelet preparations. Blood 1977; 50: 597-602
  • 10 Mills EL, Gerrard JM, Filipovich D, White JD, Quie PG. The chemiluminescence response of human platelets. J Clin Invest 1978; 61: 807-814
  • 11 Wörner P, Patscheke H. Chemiluminescence in washed human platelets during prostaglandin-thromboxane synthesis induced by N-ethylmaleimide and thimerosal. Thromb Res 1980; 19: 277-282
  • 12 Patscheke H, Wörner P. Platelet activation detected by turbidometric shape change analysis. Differential influence of cytochalasin B and prostaglandin E1 Thromb Res 1978; 12: 485-496
  • 13 Romeo D, Zabucchi G, Rossi F. Stimulation of polymorphonuclear leukocytes und macrophages by concanavalin A. Nature NB 1973; 243: 111-112
  • 14 Dutilh CE, Haddemann E, Jouvenaz GH, Ten HoorF, Nugteren DH. Study of the two pathways for arachidonate oxygenation in blood platelets. Lipids 1978; 14: 241-246
  • 15 Lapetina EG, Cuatrecasas P. Rapid inactivation of cyclooxygenase activity after stimulation of intact platelets. Proc Natl Acad Sci USA 1979; 76: 121-125
  • 16 Hamberg M, Svensson J, Samuelsson B. Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins Proc Natl Acad Sci USA 1974; 71: 3824-3828
  • 17 Mamett LJ, Wlodawer P, Samuelsson B. Co-oxygenation of organic substrates by the prostaglandin synthetase of sheep vesicular gland. J Biol Chem 1975; 250: 8510-8517
  • 18 Egan RW, Paxton J, Kuehl FA. Mechanism of irreversible self-deactivation of prostaglandin synthetase. J Biol Chem 1976; 251: 7329-7335
  • 19 Egan RW, Gale PH, Kuehl FA. Reduction of hydroperoxides in the prostaglandin biosynthetic pathway by a microsomal peroxidase. J Biol Chem 1979; 254: 3295-3302
  • 20 Moncada S, Bunting S, Mullane K, Thorogood P, Vane JR. Imidazole: a selective inhibotor of thromboxane synthetase. Prostaglandins 1977; 13: 611-618
  • 21 Needleman P, Raz A, Ferendelli JA. Application of imidazole as a selective inhibitor of thromboxane synthetase in human platelets. Proc Natl Acad Sci USA 1977; 74: 1716-1720
  • 22 Gryglewski RJ, Zmuda A, Korbut R, Krecioch E, Bieron K. Selective inhibition of thromboxane A2 biosynthesis in blood platelets. Nature (London) 1977; 267: 627-628
  • 23 Chignard M, Prancan A, Lefort J, Dray F, Vargaftig BB. Arachidonate-mediated bronchoconstriction and platelet activation are inhibited by microgram doses of compound L 8027 which are not selective for thromboxane synthetase. Agents Actions Suppl 1979; 184-187
  • 24 Takayama H, Okuma M, Uchino H. A simple method for estimation of lipoxygenase and cyclo-oxygenase pathways in human platelets - the use of thiobarbituric acid reaction. Thromb Res 1980; 44: 111-121
  • 25 Hamberg M, Samuelsson B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets Proc Natl Acad Sci USA 1974; 71: 3400-3404
  • 26 Nugteren DH. Arachidonate lipoxygenase in blood platelets. Biochim Biophys Acta 1975; 380: 299-307
  • 27 Siegel MI, McConell RT, Porter NA, Cuatrecasas P. Arachidonate metabolism via lipoxygenase and 12L-hydroperoxy-5, 8, 10, 14- eicosatetraenoic acid peroxidase sensitive to anti-inflammatory drugs. Proc Natl Acad Sci USA 1980; 77: 308-312
  • 28 Kosower NS, Kosower EM, Wertheim B. Diamide, a new reagent for the intracellular oxidation of glutathione to the disulfide. Biochem Biophys Res Commun 1969; 37: 593-598
  • 29 Bryant WR, Bailey JM. Altered lipoxygenase metabolism and decreased glutathione peroxidase activity in platelets from selenium-deficient rats. Biochem Biophys Res Commun 1980; 92: 268-276
  • 30 Lands W EM, Cook HW, Rome LH. Prostaglandin biosynthesis: consequences of oxygenase mechanism upon in vitro assays of drug effectiveness. In Advances in prostaglandin and thromboxane research Vol 1. Samuelsson P, Paoletti R. eds 1976. Raven Press; New York: 7-17
  • 31 Dutilh CE, Haddeman E, Ten Hoor F. Role of the arachidonate lipoxygenase pathway in blood platelet aggregation. In Samuelsson P, Ramwell PW, Paoletti R. eds s. S. 24 Advances in prostaglandin and thromboxane research, Vol 6. p 101-105 Raven Press; New York: 1980
  • 32 Narayanan R, Harrington MG. Hydroperoxyeicosatetraenoic acid: an activator of prostaglandin synthetase activity. Biochem Soc Transact 1980; 8: 449-450
  • 33 Blackwell GJ, Flower RJ. l-Phenyl-3-pyrazolidone: an inhibitor of cyclo-oxygenase and lipoxygenase pathways in lung and platelets. Prostaglandins 1978; 16: 417-425
  • 34 Sobanski H, Krupinska J, Cebo B, Mazur J, Kiec-Dembinska A. Antioxidants as agents potentiating the anti-inflammatory action of indomethacin. Acta Biol Med Ger 1976; 35: 1547-1551
  • 35 Panganamala RV, Miller JS, Gwebu ET, Sharma HM, Cornwell DG. Differential inhibitory effects of vitamin E and other antioxidants on prostaglandin synthetase, platelet aggregation and lipoxidase. Prostaglandins 1977; 14: 261-271
  • 36 Fiebrich F, Koch H. Silymarin, an inhibitor of prostaglandin synthetase. Experientia 1979; 35: 1550-1552
  • 37 Baumann J, Bruchhausen Fv, Wurm G. A structure-activity study on the influence of phenolic compounds and bioflavonoids on rat renal prostaglandin synthetase. Naunyn-Schmiedeberg’s Arch Pharmacol 1979; 307: 73-78
  • 38 Gerrard JM, White JG. Prostaglandins and thromboxanes “middlemen” modulating platelet function in hemostasis and thrombosis. In Spaet TH. ed Progress in hemostasis and thrombosis, Vol4. 87-125 Grune and Stratton; New York - San Francisco - London: 1978
  • 39 Fiebrich F, Koch H. Silymarin, an inhibitor of lipoxygenase. Experientia 1979; 35: 1548-1550
  • 40 Diczfalusy U, Falardeau P, Hammarström S. Conversion of prostaglandin endoperoxides to C17-hydroxy acids catalyzed by human platelets thromboxane synthetase. FEBS Lett 1977; 84: 271-274
  • 41 Cohen G. The generation of hydroxyl radicals in biologic systems: toxicological aspects. Photochem Photobiol 1978; 28: 669-675
  • 42 Cavallini L, Bindoli A, Siliprandi N. Comparative evaluation of antiperoxidative action of silymarin and other flavonoids. Pharmacol Res Commun 1978; 10: 133-136
  • 43 Paschen W, Weser U. Problems concerning the biochemical action of superoxide dismutase (erythrocuprein). Hoppe Seyler’s Z Physiol Chem 1975; 356: 727-737
  • 44 Wöraer P, Patscheke H, Paschen W. Response of platelets exposed to potassium tetraperoxochromate, an extracellular source of single oxygen, hydroxyl radicals, superoxide anions and hydrogen peroxide. Hoppe Seyler’s Z Physiol Chem 1979; 360: 559-570
  • 45 Gerrard JM, White JG, Rao GH R, Townsend D. Localization of platelet prostaglandin production in the platelet dense tubular system. Am J Pathol 1976; 83: 283-298
  • 46 Greimel A, Koch H. Silymarin - an inhibitor of horse-radish peroxidase. Experientia 1977; 33: 1417-1418