Original article| Volume 102, ISSUE 5, P788-794, November 1983

Download started.


The role of reactive oxygen species in thromboxane B2 generation by polymorphonuclear leukocytes

      This paper is only available as a PDF. To read, Please Download here.


      These studies evaluated further the relationship between the metabolism of reactive oxygen species (ROS) and prostaglandins in human granulocytes. Our experiments examined (1) the effects of several scavengers of ROS on thromboxane B2 (TXB2) production by zymosan-stimulated PMNs, (2) the capacity of the granulocytes of patients with chronic granulomatous disease (CGD) to produce TXB2, and finally (3) the generation of oxygen radicals in PMNs stimulated to produce TXB2 by the enzyme phospholipase A2. Our results confirm that both zymosan- and PMA-stimulated PMNs release increased amounts of TXB2. This enhanced production of TXB2 by normal PMNs could not be impaired and, in fact, appeared to be enhanced by scavengers of ROS. The PMNs of one patient with CGD produced TXB2 in an amount similar to those of healthy persons, whereas the TXB2 produced by the PMNs of a second patient was markedly increased. Finally, the enzyme phospholipase A2 stimulated TXB2 production in PMNs without stimulating the production of ROS. These data indicate that the activation of prostaglandin metabolism in PMNs is not dependent on the simultaneous production of ROS by these cells. However, the simultaneous production of ROS may be associated with an alteration prostaglandin metabolism.


      (ROS) (reactive oxygen species), (TXB2) (thromboxane B2), (TXA2) (thromboxane A2), (CDG) (chronic granulomatous disease), (PMN) (polymorphonuclear leukocyte), (OH·) (), hydroxyl radical (), (O2−) (superoxide), (DPBS) (Dulbecco's phosphate-buffered saline), (DMSO) (dimethyl sulfoxide), (PMA) (phorbol myristate acetate), (PGH2) (prostaglandin H2), (PGF) (prostaglandin F)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Weissmann G
        • Smolen JE
        • Korchak HM
        Release of inflammatory mediators from stimulated neutrophils.
        N Engl J Med. 1980; 303: 27
        • Klebanoff SH
        Oxygen metabolism and the toxic properties of phagocytes.
        Ann Intern Med. 1980; 93: 480
        • Weksler BB
        • Goldstein JM
        Prostaglandin: interaction with platelets and polymorphonuclear leukocytes in hemostasis and inflammation.
        Am J Med. 1980; 68: 419
        • Babior BM
        Oxygen dependent microbial killing by phagocytes.
        N Engl J Med. 1978; 298: 659
        • Spagnuolo PJ
        • Ellner JJ
        • Hassid A
        • Dunn MJ
        Thromboxane A2 mediates augmented polymorphonuclear leukocyte adhesiveness.
        J Clin Invest. 1980; 66: 406
        • Goldstein IM
        • Malmsten CL
        • Kindahl H
        • Kaplan HB
        • Radmark O
        • Samuelsson B
        • Weissmann G
        Thromboxane generation by human peripheral blood polymorphonuclear leukocytes.
        J Exp Med. 1978; 148: 787
        • Higgs GA
        • Bunting S
        • Moncada S
        • Vane JR
        Polymorphonuclear leukocytes produce thromboxane A2-like activity during phagocytosis.
        Prostaglandins. 1976; 12: 749
        • Sagone Jr, AL
        • Wells RM
        • DeMocko C
        Evidence that OH· production by human PMNs is related to prostaglandin metabolism.
        Inflammation. 1980; 4: 65
        • Sagone Jr, AL
        Effect of anti-inflammatory agents on the hydroxyl radical (OH ·) production of zymosan stimulated human granulocytes (PMNs).
        in: Rodgers MJ Powers EL Oxygen and Oxy-Radicals in Chemistry and Biology. Academic Press, Inc, New York1981
        • Egan RW
        • Paxton J
        • Kuehl Jr, FA
        Mechanism for irreversible self-deactivation of prostaglandin synthetase.
        J Biol Chem. 1976; 251: 7329
        • Egan RW
        • Gale PH
        • Kuehl Jr, FA
        Reduction of hydroperoxides in the prostaglandin biosynthetic pathway by a microsomal peroxidase.
        J Biol Chem. 1979; 254: 3295
        • Panganamala RV
        • Gavino VC
        • Cornwell DG
        Effect of low and high methional concentrations on prostaglandin biosynthesis in microsomes from bovine and sheep vesicular glands.
        Prostaglandins. 1979; 17: 155
        • Goldstein IM
        • Malmsten CL
        • Kaplan HB
        • Jindahl H
        • Samuelsson B
        • Weissmann G
        Thromboxane generation by stimulated human granulocytes: inhibition by glucocorticoids and superoxide dismutase.
        Clin Res. 1977; 25: 518
        • Panganamala RV
        • Sharma HM
        • Sprecher H
        • Geer JC
        • Cornwell DG
        A suggested role for hydrogen peroxide in the biosynthesis of prostaglandin.
        Prostaglandin. 1974; 8: 3
        • Panganamala RV
        • Sharma HW
        • Heikkila RE
        • Geer JC
        • Cornwell DG
        Role of hydroxyl radical scavengers dimethyl sulfoxide, alcohols and methional in the inhibition of prostaglandin biosynthesis.
        Prostaglandin. 1976; 11: 599
        • Mendelson D
        • Metz EN
        • Sagone Jr, AL
        The effect of phagocytosis on the reduced soluble sulfhydryl content of human granulocytes.
        Blood. 1977; 50: 1023
        • Sagone Jr, AL
        • Decker MA
        • Wells RM
        • DeMocko C
        A new method for the detection of hydroxyl radical production by phagocytic cells.
        Biochim Biophys Acta. 1980; 628: 90
        • Klassen DK
        • Sagone Jr, AL
        Evidence for both oxygen and non-oxygen dependent mechanisms of antibody sensitized target cell lysis by human monocytes.
        Blood. 1980; 56: 985
        • Klassen DK
        • Conkling P
        • Sagone Jr, AL
        Activation of monocyte and granulocyte antibody-dependent cytotoxicity by phorbol myristate acetate.
        Infect Immun. 1982; 35: 818
        • Conkling P
        • Bender G
        • Whitcomb M
        • Sagone Jr, AL
        Oxygen dependence of human alveolar macrophage-mediated antibody-dependent cytotoxicity.
        Infect Immun. 1982; 38: 114
        • Sagone Jr, AL
        • King GW
        • Metz EN
        A comparison of the metabolic response to phagocytosis in human granulocytes and monocytes.
        J Clin Invest. 1976; 57: 1352
        • Kroner EE
        • Peskar BA
        • Fischer H
        • Ferber E
        Control of arachidonic acid accumulation in bone marrow-derived macrophages by acyltransferases.
        J Biol Chem. 1981; 256: 3690
        • Sagone Jr, AL
        • Kamps S
        • Campbell R
        The effect of oxidant injury on the lymphoblastic transformation of human lymphocytes.
        Photochem Photobiol. 1978; 28: 909
        • Kraut EH
        • Sagone Jr, AL
        The effect of oxidant injury on the lymphocyte membrane and functions.
        J Lab Clin Med. 1981; 98: 697
        • Grever MR
        • Thompson V
        • Balcerzak SP
        • Sagone Jr, AL
        The effect of oxidant stress on human lymphocyte cytotoxicity.
        Blood. 1980; 56: 284
        • Koufos A
        • Sagone Jr, AL
        Effect of oxidant stress on the hexose monophosphate shunt pathway of platelets.
        Blood. 1980; 55: 835
        • Sagone Jr, AL
        • Democko C
        • Basinger L
        • Kartha M
        Determination of hydroxyl radical production in aqueous solutions irradiated to clinical significant doses.
        J Lab Clin Med. 1983; 101: 196
        • Singh DJ
        • Greenwald JE
        • Bianchine J
        • Metz EN
        • Sagone Jr, AL
        Evidence for the generation of hydroxyl radical during arachidonic acid metabolism by human platelets.
        Am J Hematol. 1981; 11: 233
        • Sagone Jr, AL
        • Greenwald J
        • Kraut EH
        • Bianchine J
        • Singh DJ
        Glucose: a role as a free radical scavenger in biological systems.
        J Lab Clin Med. 1983; 101: 97
        • Fertel R
        • Yetiv JZ
        • Coleman MA
        • Schwarz RD
        • Greenwald JE
        • Bianchine JR
        Formation of antibodies to prostaglandin in the yolk of chicken eggs.
        Biochem Biophys Res Commun. 1981; 102: 1028
        • Babior BM
        • Kipnes RS
        • Curnutte JT
        Biological defense mechanism: the production by leukocytes of superoxide, a potent bactericidal agent.
        J Clin Invest. 1973; 52: 741
        • Baehner RL
        • Murrman SK
        • Davis J
        • Johnson Jr, RB
        The role of superoxide anion and hydrogen peroxide in phagocytosis associated oxidative metabolic reactions.
        J Clin Invest. 1975; 56: 571
        • Johnston Jr, RB
        • Keele Jr, BB
        • Misra HP
        • Lehmeyer JE
        • Webb LS
        • Baehner RL
        • Rajagopalan KV
        The role of superoxide anion and generation in phagocytic bactericidal activity. Studies with normal and chronic granulomatous disease leukocytes.
        J Clin Invest. 1975; 55: 1357
        • Rosen H
        • Klebanoff S
        Chemiluminescence and superoxide production by myeloperoxidase deficient leukocytes.
        J Clin Invest. 1976; 58: 50
        • Tauber AI
        • Babior B
        Evidence for hydroxyl radical production.
        J Clin Invest. 1977; 60: 374
        • Kraut EH
        • Segal M
        • Sagone Jr, AL
        Evaluation of the role of oxygen radicals in polymorphonuclear leukocyte aggregation.
        Inflammation. 1982; 6: 161
        • Ingraham LM
        • Boxer LA
        • Baehner RL
        • Marcus AJ
        Chlorotetracycline fluorescence and arachidonic acid metabolism of polymorphonuclear leukocytes of chronic granulomatous disease patients.
        Clin Res. 1981; 29: 519A
        • Ingraham L
        • Weening R
        • Clarke M
        • Boxer LA
        • Bachner P
        Relation of respiratory burst and arachidonate metabolism during phagocytosis by guinea pig alveolar macrophages.
        J Lab Clin Med. 1982; 99: 908