The Respiratory Burst and Lymphocyte Function

  • Arthur L. SagoneJr.


Recent studies have established that phagocytic cells generate several reactive oxygen species (ROS).1–24 Normally, under resting or baseline conditions, unstimulated granulocytes and monocytes appear to release only minimal, and probably nontoxic, amounts of ROS. However, during an immunological response, phagocytic cells may have a burst in oxidative metabolism (a respiratory burst), resulting in an enhanced release of ROS at an inflammatory site.25–27 Since lymphocytes are an essential part of the inflammatory response, the potent compounds released by phagocytic cells might modify the functional capacity of these cells. This chapter discusses the possible effects of the ROS produced by phagocytic cells during the respiratory burst on the functional capacity of human lymphocytes at a site of inflammation.


Oxidative Metabolism Human Lymphocyte Phorbol Myristate Acetate Respiratory Burst Chronic Granulomatous Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Klebanoff SJ: Antimicrobial mechanism in neutrophilic polymorphonuclear leukocytes. Semin Hematol 12: 117–142, 1975.PubMedGoogle Scholar
  2. 2.
    Babior BM: The respiratory burst of phagocytes. J Clin Invest 73: 559–601, 1984.Google Scholar
  3. 3.
    Johnston RB, Lehmeyer JE: Elaboration of toxic oxygen by-products by neutrophils in a model of immune complex disease. J Clin Invest 51: 836–841, 1976.Google Scholar
  4. 4.
    Babior BM, Kipnes R, Curnette JT: Biological defense mechanisms. The production of leukocytes of superoxide, a potential bactericidal agent. J Clin Invest 52: 741–744, 1973.PubMedGoogle Scholar
  5. 5.
    Johnston RB Jr, Keele BB, Misra HP, et al: The role of superoxide anion generation in phagocytic bactericidal activity—Studies with normal and chronic granulomatous disease leukocytes. J Clin Invest 55: 1357–1372, 1975.PubMedGoogle Scholar
  6. 6.
    Lehmeyer JE, Johnston RB Jr: Effect of anti-inflammatory drugs and agents that elevate intra-cellular cyclic AMP on the release of toxic oxygen metabolites by phagocytes: Studies in a model of tissue-bound IgG. Clin Immunol Immunopathol 9: 482–490, 1978.PubMedGoogle Scholar
  7. 7.
    Iyer GY, Islam MF, Quastel JH: Biochemical aspect of phagocytosis. Nature (Lond.) 192: 535–541, 1961.Google Scholar
  8. 8.
    Sbarra AJ, Karnovsky ML: The biochemical basis of phagocytosis I, Metabolic changes during the ingestion of particles by polymorphonuclear leukocytes. J Biol Chem 234: 1355–1362, 1959.PubMedGoogle Scholar
  9. 9.
    Karnovsky ML: Metabolic basis of phagocytic activity. Physiol Rev 42: 143–168, 1962.PubMedGoogle Scholar
  10. 10.
    Curnette JT, Babior B: Biological defense mechanisms, the effect of bacteria and serum on superoxide production by granulocyte. J Clin Invest 53: 1662–1672, 1974.Google Scholar
  11. 11.
    Homan-Muller J, Weening RS, Roos D: Production of hydrogen peroxide by phagocytosing human granulocytes J Lab Clin Med 85: 198–207, 1975.Google Scholar
  12. 12.
    Allen RC, Stjernholm R, 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 47: 679–684, 1972.PubMedGoogle Scholar
  13. 13.
    Webb LS, Keele BB Jr, Johnston RB Jr: Inhibition of phagocytosis-associated chemiluminescence by superoxide dismutase. Infect Immun 9: 1051–1056, 1974.PubMedGoogle Scholar
  14. 14.
    Baehner RL, Murrman SK, Davis J, et al: The role of superoxide anion and hydrogen peroxide in phagocytosis-associated oxidative metabolic reactions. J Clin Invest 56: 571–576, 1975.PubMedGoogle Scholar
  15. 15.
    Sagone AL Jr, King GW, Metz EN: A comparison of the metabolic responses to phagocytosis in human granulocytes and monocytes. J Clin Invest 57: 1352–1358, 1976.PubMedGoogle Scholar
  16. 16.
    Klebanoff SJ, Pincus SH: Hydrogen peroxide utilization in myeloperoxidase-deficient leukocytes: A possible microbicidal control mechanism. J Clin Invest 50: 2226–2229, 1971.PubMedGoogle Scholar
  17. 17.
    Weening RS, Roos P, Loos J A: Oxygen consumption of phagocytizing cells in human leukocyte and granulocyte preparations: A comparative study. J Lab Clin Med 83: 570–576, 1974.PubMedGoogle Scholar
  18. 18.
    Root RK, Metcalf J, Oshino N: H202 release from human granulocytes during phagocytosis. I. Documentation, quantitation, and some regulating factors. J Clin Invest 55: 945–955, 1975.PubMedGoogle Scholar
  19. 19.
    Tsan Min Fu, Chen JW: Oxidation of methionine by human polymorphonuclear leukocyte. J Clin Invest 65: 1041–1050, 1980.Google Scholar
  20. 20.
    Weiss SJ, Klein R, Slivka A, et al: Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation. J Clin Invest 70: 598–607, 1982.PubMedGoogle Scholar
  21. 21.
    Thomas EL, Grisham MB, Jefferson MM: Myeloperoxidase-dependent effect of amines on func-tion of isolated neutrophils. J Clin Invest 72: 441–454, 1983.PubMedGoogle Scholar
  22. 22.
    Weiss SJ, Lambert MD, Test ST: Long-lived oxidants generated by human neutrophils: Charac-teristics and bioactivity. Science 222: 625–628, 1983.PubMedGoogle Scholar
  23. 23.
    Sagone AL Jr, Husney RM, O’Dorisio MS, et al: Mechanisms for the oxidation of reduced glutathione by zymosan stimulated granulocytes. Blood 63: 96–104, 1984.PubMedGoogle Scholar
  24. 24.
    Pincus S, Klebanoff SJ: Quantitative leukocyte iodination. N Engl J Med 284: 744–750, 1984.Google Scholar
  25. 25.
    McCord J: Free Radicals and inflammation: Protection of synovial fluid by superoxide dismutase. Science 185: 529–531, 1974.PubMedGoogle Scholar
  26. 26.
    Oxygen free radicals and tissue damage, in Fitzsimons DW (ed): Ciba Foundation Symposium 65, Excerpta Medica Amsterdam, New York, 1979, 1–381.Google Scholar
  27. 27.
    Weissman G, Smolen JE, Korchak EM: Release of inflammatory mediators from stimulated neutrophils. N Engl J Med 303: 27–34, 1980.Google Scholar
  28. 28.
    Weissman G, Serhan C, Korchak HM, et al: Neutrophils generate phosphatidic acid, an endogenous calcium ionophore: Before releasing mediators of inflammation. Trans Assoc Am Phys 94: 357–365, 1981.Google Scholar
  29. 29.
    Boxer LA, Yoder M, Bonsib S, et al: Effect of a chemotactic factor, N-formylmethionyl peptide on adherence, superoxide anion generation, phagocytosis and microtubule assembly of human polymorphonuclear leukocytes. J Lab Clin Med 93: 506–514, 1979.PubMedGoogle Scholar
  30. 30.
    Koretzky GA, Daniele RP, Nowell PC: A phorbol ester (TPA) can replace macrophages in human lymphocyte cultures stimulated with a mitogen but not with an antigen. J Immunol 128: 1776–1780, 1982.PubMedGoogle Scholar
  31. 31.
    Simon PL, Willoughby WF: The role of subcellular factors in pulmonary immune function: Physicochemical characterization of two distinct species of lymphocyte-activating factor produced by rabbit alveolar macrophages. J Immunol 126: 1534–1541, 1981.PubMedGoogle Scholar
  32. 32.
    Goldstein IM, Roos D, Kaplan HB, Weissman G: Complement and immunoglobulin stimulate superoxide production by human leukocytes independently of phagocytosis. J Clin Invest 56: 1155–1163, 1975.PubMedGoogle Scholar
  33. 33.
    Henson PM, Oades ZG: Stimulation of human neutrophils by soluble and immunoglobin aggre-gates—Secretion of granule constituents and increased oxidation of glucose. J Clin Invest 56: 1053–1061, 1975.PubMedGoogle Scholar
  34. 34.
    Weksler BB, Goldstein IM: Prostaglandin: Interactions with platelets and polymorphonuclear leukocytes in hemostasis and inflammation. Am J Med 68: 419–428, 1980.PubMedGoogle Scholar
  35. 35.
    Segal ML, Fertel RH, Kraut EH, Sagone AL: The role of reactive oxygen species in thromboxane B2 generation by polymorphonuclear leukocytes. J Lab Clin Med 102: 788–794, 1983.PubMedGoogle Scholar
  36. 36.
    Goldstein IM, Malmsten CL, Kindahl H, et al: Thromboxane generation by human neutrophils polymorphonuclear leukocytes. J Exp Med 148: 787–792, 1978.PubMedGoogle Scholar
  37. 37.
    Mallery SR, Zeligs BJ, Ramwell PW, Bellanti JA: Gender-related variations of human neutrophil cyclo-oxygenase and oxidative burst metabolites. J Leukocyte Biol 40: 133–148, 1986.PubMedGoogle Scholar
  38. 38.
    Sagone AL Jr, Decker MA, Wells RM, Democko C: A new method for the detection of hydroxyl radical production. Biochim Biophys Acta 628: 90–97, 1980.PubMedGoogle Scholar
  39. 39.
    Alexander MS, Husney RM, Sagone AL Jr: Metabolism of benzoic acid by stimulated poly-morphonuclear cells. Biochem Pharmacol 35: 3649–3651, 1986.PubMedGoogle Scholar
  40. 40.
    Sagone AL, Husney RM: Oxidation of salicylates by stimulated granulocytes—Evidence that these drugs act as free radical scavengers in biological systems. J Immunol 138: 1–7, 1987.Google Scholar
  41. 41.
    Sagone AL, Husney R, Guter H, Clark L: The effect of catalase on the proliferation of human lymphocytes to phorbol myristate acetate. J Immunol 133: 1488–1494, 1984.PubMedGoogle Scholar
  42. 42.
    Repine JE, Eaton JW, Anders MW, et al: Generation of hydroxy 1 radicals by enzymes, chemicals, and human phagocytes in vitro. Detection with the anti-inflammatory agent, dimethyl sulfoxide. J Clin Invest 64: 1642–1651, 1979.PubMedGoogle Scholar
  43. 43.
    Klassen D, Conkling P, Sagone AL: Activation of monocyte and granulocyte antibody-dependent cytotoxicity by phorbol myristate acetate. Infect Immun 35: 818–825, 1982.PubMedGoogle Scholar
  44. 44.
    Papermaster-Bender G, Whitcomb M, Sagone AL Jr: Characterization of the metabolic responses of human pulmonary alveolar macrophage. J Reticulendothel Soc 28: 129–139, 1980.Google Scholar
  45. 45.
    Seaman WE, Gindhart TD, Blackman MA, et al: Suppression of natural killing in vitro by monocytes and polymorphonuclear leukocytes. J Clin Invest 69: 876–888, 1982.PubMedGoogle Scholar
  46. 46.
    Zoschke DC, Messner RP: Suppression of human lymphocyte mitogenesis mediated by phagocyte-released reactive oxygen species: comparative activities in normals and in chronic granulomatous disease. Clin Immunol Immunopathol 32: 29–40, 1984.PubMedGoogle Scholar
  47. 47.
    Pryzwansky KB, Martin LE, Spitznagel JK: Immunocytochemical localization of myeloperoxidase, lactoferrin, lysozyme and neutral proteases in human monocytes and neutrophilic granulocytes. J Reticuloendothel Soc 24: 295–309, 1978.PubMedGoogle Scholar
  48. 48.
    Zabos P, Kyner D, Mendelsohn N, et al: Catabolism of 2-deoxyglucose by phagocytic leukocytes in the presence of 12-0-tetradecanoyl phorbol-13-acetate. Proc Natl Acad Sci USA 75: 5422–5426, 1978.PubMedGoogle Scholar
  49. 49.
    Nathan CF, Brukner LH, Silverstein SC, et al: Extracellular cytolysis by activated macrophages and granulocytes. I. Pharmacologic triggering of effector cells and the release of hydrogen peroxide. J Exp Med 49: 84–99, 1979.Google Scholar
  50. 50.
    Murray HW, Juangbhanich CW, Nathan CF, et al: Macrophage oxygen-dependent antimicrobial activity. J Exp Med 150: 950–964, 1979.PubMedGoogle Scholar
  51. 51.
    Cohen MS, Taffet ST, Adams DO: The relationship between competence for secretion of H2O2 and completion of tumor cytotoxicity by BCG-elicited murine marcophages. J Immunol 128: 1781–1785, 1982.PubMedGoogle Scholar
  52. 52.
    Saito H, Tomioka H, Watanabe T: H202 releasing function of macrophages activated with various mycobacteria based on wheat germ agglutinin and phorbol myristate acetate triggering. J Re-ticuloendothel Soc 29: 193–204, 1981.Google Scholar
  53. 53.
    Pennline KJ, Herscowitz HB: Dual role for alveolar macrophages in humoral and cell-mediated immune responses: evidence for suppressor and enhancing functions. J Reticuloendothel Soc 30: 205–217, 1981.PubMedGoogle Scholar
  54. 54.
    Drath DB, Karnovsky ML, Huber GL: Hydroxyl radical formation in phagocytic cells of the rat. J Appl Physiol 46: 136–140, 1979.PubMedGoogle Scholar
  55. 55.
    Heifets L, Imai K, Goren MB: Expression of peroxidase-dependent iodination by macrophages ingesting neutrophil debris. J Reticuloendothel Soc 28: 391–404, 1980.PubMedGoogle Scholar
  56. 56.
    Hoidal J, Repine J, Beall G et al: The effect of phorbol myristate acetate on the metabolism and ultrastructure of alveolar macrophages. Am J Pathol 91: 469–476, 1978.PubMedGoogle Scholar
  57. 57.
    Murray H, Cohn Z: Macrophage oxygen-dependent antimicrobial activity III Enhanced oxidative metabolism as an expression of macrophage activation. J Exp Med 152: 1596–1609, 1980.PubMedGoogle Scholar
  58. 58.
    North RJ: Opinions: The concept of the activated macrophage. J Immunol 121: 806–816, 1978.PubMedGoogle Scholar
  59. 59.
    Turpin J, Hersh EM, Lopez-Berestein G: Characterization of small and large human peripheral blood monocytes: effects of in vitro maturation on hydrogen peroxide release and on the response to macrophage activators. J Immunol 136: 4194–4198, 1986.PubMedGoogle Scholar
  60. 60.
    Montarroso AM, Myrvik QN: Oxidative metabolism of BCG-activated alveolar macrophages. J Reticuloendothel Soc 25: 559–574, 1979.PubMedGoogle Scholar
  61. 61.
    Douglas SD: Macrophage nomenclature: Where are we going? J Reticuloendothel Soc 27: 241–245, 1980.Google Scholar
  62. 62.
    Breton-Gorius J, Guichard J, Vainchenker W, et al: Ultrastructural and cytochemical changes induced by short and prolonged culture of human monocytes. J Reticuloendothel Soc 27: 289–301, 1980.PubMedGoogle Scholar
  63. 63.
    Anderson SE Jr, Remington JS: Effect of normal and activated human macrophages on toxoplasma gondii. J Exp Med 139: 1154–1173, 1974.PubMedGoogle Scholar
  64. 64.
    Karnovsky ML, Simmons S, Glass EA: Metabolism of macrophages, in Van Furth R (ed): Mono-nuclear Phagocytes Philadelphia, F. A. Davis, 1970, p 103–120.Google Scholar
  65. 65.
    Musson RA, Shafran H, Henson PM: Intracellular levels and stimulated release of lysosomal enzymes from human peripheral blood monocytes and monocyte-derived macrophages. J Re-ticuloendothel Soc 28: 249–264, 1980.Google Scholar
  66. 66.
    Rosenthal AS: Medical intelligence. Current concepts: Regulation of the immune response—Role of the macrophage. N Engl J Med 303: 1153–1156, 1980.PubMedGoogle Scholar
  67. 67.
    Speert DP, Silverstein SC: Phagocytosis of unopsonized zymosan by human monocyte-derived macrophages: Maturation and inhibition by mannan. J Leukocyte Biol 38: 655–658, 1985.PubMedGoogle Scholar
  68. 68.
    Soler P, Basset F, Mazin F, et al: Peroxidatic activities of human alveolar macrophages in some pulmonary granulomatous disorders. J Reticuloendothel Soc 31: 511–521, 1982.PubMedGoogle Scholar
  69. 69.
    Gately CL, Wahl SM, Oppenheim JJ: Characterization of hydrogen peroxide-potentiating factor. A lymphokine that increases the capacity of human monocytes and monocyte-like cell lines to produce hydrogen peroxide. J Immunol 131: 2853–2858, 1983.PubMedGoogle Scholar
  70. 70.
    Chapes SK, Haskill S: Synergistic effect between neutrophils and corynebacterium parvum in the process of macrophage activation. Cancer Res 44: 31–34, 1984.PubMedGoogle Scholar
  71. 71.
    Weisbart RH, Kwan L, Golde DW: Human GM-CSF primes neutrophils for enhanced oxidative metabolism in response to the major physiological chemoattractants. Blood 69: 18–21, 1987.PubMedGoogle Scholar
  72. 72.
    Nathan CF, Murray HW, Wiebe ME, et al: Identification of interferon-7 as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158: 670–689, 1983.PubMedGoogle Scholar
  73. 73.
    Wilson ME, Jones DP, Munkenbeck P, et al: Serum-dependent and independent effects of bacterial lipopolysaccharides on human neutrophil oxidative capacity in vitro. J Reticuloendothel Soc 31: 43–57, 1982.PubMedGoogle Scholar
  74. 74.
    Nakagawara, A, Desantis NM, Nogueira N, et al: Lymphokines enhance the capacity of human monocytes to secrete reactive oxygen intermediates. J Clin Invest 70: 1042–1048, 1982.PubMedGoogle Scholar
  75. 75.
    Sagone AL Jr, LoBuglio AT, Balcerzak SP: Alteration in hexose monophosphate shunt during lymphoblastic transformation. Cell Immunol 14: 443–452, 1974.PubMedGoogle Scholar
  76. 76.
    Hadden JW, Hadden EM, Good RA: Adrenergic mechanisms in human lymphocyte metabolism. Biochim Biophysic Acta 237: 330–347, 1971.Google Scholar
  77. 77.
    Roos D, Loos JA: Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes. Biochim Biophys Acta 222: 565–582, 1970.PubMedGoogle Scholar
  78. 78.
    Stjernholm RL: Early biochemical changes in phytohemagglutinin-stimulated human lymphocytes of blood and lymph. J Reticuloendothel Soc 7: 471–483, 1970.PubMedGoogle Scholar
  79. 79.
    Novogrodsky A, Ravid A, Rubin A, et al: Hydroxy 1 radical scavengers inhibit lymphocyte mitogenesis. Proc Natl Acad Sei USA 79: 1171–1174, 1982.Google Scholar
  80. 80.
    Duwe AK, Werkmeister J, Roder JC: Natural killer cell–mediated lysis involves an hydroxyl radical-dependent step. J Immunol 134: 2637–2644, 1985.PubMedGoogle Scholar
  81. 81.
    Mookerjee BK, Wakerle H, Sharon N, et al: Chemiluminescence and lymphocyte proliferation: parallelism in collaboration between subpopulations of thymus cells for both types of responses. J Leukocyte Biol 35: 427–438, 1984.PubMedGoogle Scholar
  82. 82.
    Kurlander RJ, Rosse WF, Logue GL: Quantitative influence of antibody and complement coating of red cells on monocyte-mediated cell lysis. J Clin Invest 61: 1309–1319, 1978.PubMedGoogle Scholar
  83. 83.
    Adler R, Glorioso JC, Cossman J, et al: Possible role of Fc receptors on cells infected and transformed by herpesvirus: Escape from immune cytolysis. Infect Immun 21: 442–447, 1978.PubMedGoogle Scholar
  84. 84.
    Ehlenberger AG, Nussenzweig V: The role of membrane receptors for C3b and C3d in phagocyto-sis. J Exp Med 145: 357–371, 1977.PubMedGoogle Scholar
  85. 85.
    Wuest D, Crane R, Rinehart JJ: Enhancement of Fc receptor function during human monocyte differentiation in vitro. J Reticuloendothel Soc 30: 147–155, 1981.PubMedGoogle Scholar
  86. 86.
    Newman SL, Becker S, Halme J: Phagocytosis by receptors for C3b (CRj), iC3b, (CR3), and IgG (Fc) on human peritoneal macrophages. J Leukocyte Biol 38: 267–278, 1985.PubMedGoogle Scholar
  87. 87.
    Leijh PC, Van Den Barselaar M, van Zwet TL, et al: Requirement of extracellular complement and immunoglobulin for intracellular killing of micro–organisms by human monocytes. J Clin Invest 63: 772–784, 1979.PubMedGoogle Scholar
  88. 88.
    Lawrence DA, Weigle WO, Spiegelberg HL: Immunoglobulins cytophilic for human lymphocytes, monocytes, and neutrophils. J Clin Invest 55: 368–376, 1975.PubMedGoogle Scholar
  89. 89.
    Whaley K: Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral blood monocytes. J Exp Med 151: 501–516, 1980.PubMedGoogle Scholar
  90. 90.
    Shigeoka AO, Hall RT, Hemming VG, et al: Role of antibody and complement in opsonization of group B streptococci. Infect Immun 21: 34–40, 1978.PubMedGoogle Scholar
  91. 91.
    Wardley RC, Rouse BT, Babiuk LA: Antibody dependent cytotoxicity mediated by neutrophils: A possible mechanism of antiviral defense. J Reticuloendothel Soc 19: 323–332, 1976.PubMedGoogle Scholar
  92. 92.
    Brogen M, Sagone AL Jr: The metabolic response of human phagocytic cells to killed mumps particles. J Reticulothel Soc 27: 13–22, 1980.Google Scholar
  93. 93.
    Katz P, Simone CB, Henkart PA, et al: Mechanisms of antibody-dependent cellular cytotoxicity. J Clin Invest 65: 55–63, 1980.PubMedGoogle Scholar
  94. 94.
    Clark RA, Klebanoff SJ: Studies on the mechanism of antibody-dependent polymorphonuclear leukocyte-mediated cytotoxicity. J Immunol 119: 1413–1418, 1977.Google Scholar
  95. 95.
    Borregaard N, Kragballe K: Role of oxygen in antibody-dependent cytotoxicity mediated by monocytes and macrophages. J Clin Invest 66: 676–683, 1980.PubMedGoogle Scholar
  96. 96.
    Seim S, Espevik T: Toxic oxygen species in monocyte-mediated antibody-dependent cytotoxicity. J Reticuloendothel Soc 33: 417–428, 1983.PubMedGoogle Scholar
  97. 97.
    Hafqman DG, Lucas ZJ: Polymorphonuclear leukocyte-mediated, antibody-dependent, cellular cytotoxicity against tumor cells: Dependence on oxygen and the respiratory burst. J Immunol 123: 55–62, 1979.Google Scholar
  98. 98.
    Storkus WJ, Dawson JR: Oxygen-reactive metabolites are not detected at the effector-target interface during natural killing. J Leukocyte Biol 39: 547–557, 1986.PubMedGoogle Scholar
  99. 99.
    Klassen DK, Sagone AL Jr: Evidence for both oxygen and non-oxygen dependent mechanisms of antibody sensitized target cell lysis by human monocytes. Blood 56: 985–992, 1980.PubMedGoogle Scholar
  100. 100.
    Archibald AC, Cheung K, Robinson MF: The interaction of lymphocyte surface-bound immune complexes and neutrophils. J Immunol 131: 207–211, 1983.PubMedGoogle Scholar
  101. 101.
    Sacks T, Moldow CF, Craddock PR, et al: Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes an in vitro model of immune vascular damage. J Clin Invest 61: 1161–1167, 1978.PubMedGoogle Scholar
  102. 102.
    Till GO, Johnson RJ, Kunkel R, Ward PA: Intravascular activation of complement and acute lung injury. J Clin Invest 69: 1126–1135, 1982.PubMedGoogle Scholar
  103. 103.
    Ward PA, Till, Kunkel R, Et Al: Evidence of role of hydroxy 1 radical in complement and neu-trophil-dependent tissue injury. J Clin Invest 72: 789–801, 1983.PubMedGoogle Scholar
  104. 104.
    Cooke E, Hallett MB: The role of C-kinase in the physiological activation of the neutrophil oxidase. Biochem J 232: 323–327, 1985.PubMedGoogle Scholar
  105. 105.
    van der Meulen FW, van der Hart M, Fleer A, et al: The role of adherence to human mononuclear phagocytes in the destruction of red cells sensitized with non-complement binding IgG antibodies. Br J Haematol 38: 541–549, 1978.PubMedGoogle Scholar
  106. 106.
    Conkling PR, Klassen DK, Sagone AL: Comparison of antibody-dependent cytotoxicity mediated by human polymorphonuclear cells, monocytes, alveolar macrophages. Blood 60: 1290–1297, 1982.PubMedGoogle Scholar
  107. 107.
    Lee D, Hoidal J, Garlich D et al: Opsonin-independent phagocytosis of surface-adherent bacteria by human alveolar macrophages. J Leukocyte Biol 36: 689–701, 1984.PubMedGoogle Scholar
  108. 108.
    Eissenberg LG, Goldman WE: Histoplasma capsulatum fails to trigger release of superoxide from macrophages. Infect Immun 55: 29–34, 1987.PubMedGoogle Scholar
  109. 109.
    Abramson JS, Mills EL, Giebink GS, et al: Depression of monocyte and polymorphonuclear leukocyte oxidative metabolism and bactericidal capacity by influenza virus. Infect Immun 35: 350–355, 1982.PubMedGoogle Scholar
  110. 110.
    Copeland E, Rinehart J, Lewis M, et al: The mechanism of retrovirus suppression of T cell proliferation. J Immunol 131: 2017–2020, 1983.Google Scholar
  111. 111.
    Anderson V, Hellung-Larsen FP, Shrenson SF: Optimal oxygen tension for human lymphocytes in culture. J Cell Physiol 72: 149–152, 1968.Google Scholar
  112. 112.
    Anderson V, Anderson AB, Skovbjerg H, et al: Structure of mitochondria in lymphocytes culture at different oxygen tensions. Acta Pathol Microbiol Scand [A] 78: 537–544, 1970.Google Scholar
  113. 113.
    Mizrahi A, Vosseller GV, Yagi Y, et al: The effect of dissolved oxygen partial pressure on growth, metabolism and immunoglobulin production in a permanent human lymphocyte cell line culture. Proc Soc Exp Biol Mod 139: 118–122, 1972.Google Scholar
  114. 114.
    Kilburn DG, Morley M, Yensen J: The influence of dissolved oxygen on the mitogen responses of mouse lymphocytes. J Cell Physiol 87: 307–311, 1975.Google Scholar
  115. 115.
    Sagone AL Jr: Effect of hyperoxia on the carbohydrate metabolism of human lymphocytes. Am J Hematol 18: 269–274, 1985.PubMedGoogle Scholar
  116. 116.
    Rabinowitz Y, Lubrano T, Wilhite BA, et al: Lactic dehydrogenase of cultured lymphocytes: Response to environmental conditions. Exp Cell Res 48: 675–678, 1967.Google Scholar
  117. 117.
    Fridovich I: The biology of oxygen radicals. Science 201: 875–880, 1978.PubMedGoogle Scholar
  118. 118.
    Harlan JM, Levine JD, Callahan KS, et al: Glutathione Redox cycle protects cultured endothelial cells against lysis by extracellularly generated hydrogen peroxide. J Clin Invest 73: 706–713, 1984.PubMedGoogle Scholar
  119. 119.
    Arrick BA, Nathan CF, Cohn ZA: Inhibition of glutathione synthesis augments lysis of murine tumor cells by sulfhydryl-reactive antineoplastics. J Clin Invest 71: 258–267, 1983.PubMedGoogle Scholar
  120. 120.
    Stankova L, Rigas DA, Keown P, et al: Leukocyte ascorbate and glutathione: Potential capacity for inactivating oxidants and free radicals. J Reticuloendothel Soc 21: 97–102, 1977.PubMedGoogle Scholar
  121. 121.
    Marklund S, Nordensson I, Back O: Normal CuZn superoxide dismutase, Mn superoxide dis-mutase, catalase and glutathione peroxidase in Werner’s syndrome. J Gerontol 36: 405–409, 1981.PubMedGoogle Scholar
  122. 122.
    Meerhof LJ, Roos D: An easy, specific and sensitive assay for the determination of the catalase activity of human blood cells. J Reticuloendothel Soc 28: 419–425, 1980.PubMedGoogle Scholar
  123. 123.
    Arrick B, Nathan C: Glutathione metabolism as a determinant of therapeutic efficacy. A review. Cancer Res. 44: 4224–4232, 1984.PubMedGoogle Scholar
  124. 124.
    Roos D, Weening R, Voetman A, et al: Protection of phagocytic leukocytes by exogenous glutathione: studies in a family with glutathione deficiency reductase deficiency. Blood 53: 851–866, 1979.PubMedGoogle Scholar
  125. 125.
    Spielberg SP, Boxer LA, Oliver JM, et al: Oxidative damage to neutrophils in glutathione synthetase deficiency. Br J Haematol 42: 215–223, 1979.PubMedGoogle Scholar
  126. 126.
    Freeman BA, Crapo JD: Biology of disease-free radicals and tissue injury. Lab Invest 47: 412–426, 1982.PubMedGoogle Scholar
  127. 127.
    Chance B, Sies H, Boveris A: Hydroperoxide metabolism in mammalian organs. Physiol Rev 59: 527–605, 1979.PubMedGoogle Scholar
  128. 128.
    Baral E, Blomgen H: Response of human lymphocytes to mitogenic stimuli after irradiation in vitro. Acta Radiol Ther Phys Biol 15: 149–161, 1976.PubMedGoogle Scholar
  129. 129.
    Braeman J, Moore J: The lymphocyte response to phytohemagglutinin after in vitro radiation. Br J Radiol 47: 297, 1974.PubMedGoogle Scholar
  130. 130.
    Roberts W, Kartha M, Sagone AL Jr: Effect of irradiation on the hexose monophosphate shunt pathway of human lymphocytes. Radiat Res 79: 601–610, 1979.PubMedGoogle Scholar
  131. 131.
    Wasserman J, Petrini B, Blomgren H: Radiosensitivity of T-lymphocyte subpopulations. J Clin Lab Immunol 8: 139–140, 1982.Google Scholar
  132. 132.
    Kleinerman ES, Decker JM, Muchmore AV: In vitro cellular regulation of monocyte function: Evidence for a radiosensitive suppressor. J Reticuloendothel Soc 30: 373–380, 1981.PubMedGoogle Scholar
  133. 133.
    Stefani S, Kerman R: Lymphocyte response to phytohemagglutinin before and after radiation therapy in patients with carcinomas of the head and neck. J Laryngol Otol 91: 605–610, 1977.PubMedGoogle Scholar
  134. 134.
    Anderson RE, Standefer JC, Scaletti JV: Radiosensitivity of defined populations of lymphocytes. Cell Immun 33: 45–61, 1977.Google Scholar
  135. 135.
    Merz T, Hazra T, Ross M, et al: Transformation delay of lymphocytes in patients undergoing radiation therapy. AJR 127: 337–339, 1976.PubMedGoogle Scholar
  136. 136.
    Howard-Flanders P, Levin J, Theriot L: Reactions of DNA radicals with sulfhydryl in x-irradiated bacteriophage systems. Radiat Res 18: 593–606, 1963.PubMedGoogle Scholar
  137. 137.
    Goscin S, Fridovich I: Superoxide dismutase and the oxygen effect. Radiat Res 56: 565–569, 1973.PubMedGoogle Scholar
  138. 138.
    Scholes G, Weiss J: Oxygen effects and formation of peroxides in aqueous solution. Radiat Res 1 (suppl):177–189, 1959.Google Scholar
  139. 139.
    Oberley L, Lindgren A, Baker Et Al: Superoxide ion and the cause of the oxygen effect. Radiat Res 68: 320–328, 1976.PubMedGoogle Scholar
  140. 140.
    Lavelle F, Michelson M, Mitrijene: Biological protection by superoxide dismutase. Biochem Biophys Res Commun 55: 350–357, 1973.PubMedGoogle Scholar
  141. 141.
    Konings AWT, Oosterloo SK: Radiation effects on membranes. Radiat Res 81: 200–207, 1980.PubMedGoogle Scholar
  142. 142.
    Stankova L, Rigas D, Head C, et al: Determinants of resistance to radiation injury in blood granulocytes from normal donors and from patients with myeloproliferative disorders. Radiat Res 80: 49–60, 1979.PubMedGoogle Scholar
  143. 143.
    Edsmyr F, Huber W, Menander KB: Orgotein efficacy in ameliorating side effects due to radiation therapy. Current Ther Res 19: 198–211, 1976.Google Scholar
  144. 144.
    Westman G, Marklund SL: Diethyldithiocarbamate, a superoxide dismutase inhibitor, decreases the radioresistance of Chinese hamster cells. Radiat Res 83: 303–311, 1980.PubMedGoogle Scholar
  145. 145.
    McLennan G, Oberley LW, Autor AP: The role of oxygen-derived free radicals in radiation-induced damage and death of nondividing eucaryotic cells. Radiat Res 84: 122–132, 1980.PubMedGoogle Scholar
  146. 146.
    Kiefer J: Does singlet oxygen contribute to the oxygen effect. Int J Radiat Biol 34: 587–588, 1978.Google Scholar
  147. 147.
    Helf KD: Interactions of radioprotectors and oxygen in cultured mammalian cells. Radiat Res 101: 424–433, 1985.Google Scholar
  148. 148.
    Russo A, Mitchell JB, Finkelstein E, et al: The effects of cellular glutathione elevation on the oxygen enhancement ratio. Radiat Res 103: 232–239, 1985.PubMedGoogle Scholar
  149. 149.
    Morse M, Dahl R: Cellular glutathione is a key to the oxygen effect in radiation damage. Nature (Lond) 271: 660–662, 1978.Google Scholar
  150. 150.
    Sagone AL Jr: Role of the hexose monophosphate shunt in cellular protection against radiation damage, in Rodgers M, Powers E (ed): Oxygen and Oxy-radicals in Chemistry and Biology. New York, Academic, 1981, pp 725–729.Google Scholar
  151. 151.
    O’Brien RL, Parker JW: Oxidation-Induced lymphocyte transformation. Cell 7: 13–20, 1976.PubMedGoogle Scholar
  152. 152.
    Novogrodsky A, Katchalski E: Membrane site modified on induction of the transformation of lymphocytes by periodate. Proc Natl Acad Sci USA 69: 3207–3210, 1972.PubMedGoogle Scholar
  153. 153.
    Biniaminov M, Ramot B, Novogrodsky A: Effect of macrophages on periodate-induced transformation of normal and chronic lymphatic leukaemia lymphocytes. Clin Exp Immunol 16: 235–242, 1974.Google Scholar
  154. 154.
    Monahan TM, Fritz RR, Abell CW: Sodium periodate stimulation of normal and chronic lymphocytic leukemia lymphocytes. Exp Cell Res 103: 263–269, 1976.PubMedGoogle Scholar
  155. 155.
    Roffman E, Wilchek M: The extent of oxidative mitogenesis does not correlate with the degree of aldehyde formation of the T lymphocyte membrane. J Immunol 137: 40–44, 1986.PubMedGoogle Scholar
  156. 156.
    Sagone AL Jr, Kamps S, Campbell R: The effect of oxidant injury on the lymphoblastic transformation of human lymphocytes. Photochem Photobiol 28: 909–915, 1978.PubMedGoogle Scholar
  157. 157.
    Lipsky PE: Immunosuppression by D-penicillamine in vitro. J Clin Invest 73: 53–65, 1984.PubMedGoogle Scholar
  158. 158.
    El-Hag A, Lipsky PE, Bennett M, et al: Immunomodulation by neutrophil myeloperoxidase and hydrogen peroxide: Differential susceptibility of human lymphocyte functions. J Immunol 136: 3420–3426, 1986.PubMedGoogle Scholar
  159. 159.
    El-Hag A, Clark RA: Down-regulation of human natural killer activity against tumors by the neutrophil myeloperoxidase system and hydrogen peroxide. J Immunol 133: 3291–3297, 1984.PubMedGoogle Scholar
  160. 160.
    Grever MR, Thompson VN, Balcerzak SP, Sagone AL Jr: The effect of oxidant stress on human lymphocyte cytotoxicity. Blood 56: 284–288, 1980.PubMedGoogle Scholar
  161. 161.
    Whisler RL, Newhouse YG: Inhibition of human B lymphocyte colony responses by endogenous synthesized hydrogen peroxide and prostaglandins. Cell Immunol 69: 34–45, 1982.PubMedGoogle Scholar
  162. 162.
    Kraut EH, Sagone AL Jr: The effect of oxidant injury on the lymphocyte membrane and functions. J Lab Clin Med 98: 697–703, 1981.PubMedGoogle Scholar
  163. 163.
    Sugar AM, Chahal RS, Brummer E, et al: The iron-hydrogen peroxide-iodide system is fungicidal: Activity against the yeast phase of blastomyces dermatitidis. J Leukocyte Biol 36: 545–548, 1984.PubMedGoogle Scholar
  164. 164.
    Clark RA, Klebanoff SJ, Einstein AB, et al: Peroxidase-H202-halide system: Cytotoxic effect on mammalian tumor cells. Blood 45: 161–170, 1975.PubMedGoogle Scholar
  165. 165.
    Weiss SJ: The role of superoxide in the destruction of erythrocyte targets by human neutrophils. J Biol Chem 255: 9912–9917, 1980.PubMedGoogle Scholar
  166. 166.
    Weiss SJ: Oxidative autoactivation of latent collangenase by human neutrophils. Science 227: 747–749, 1985.PubMedGoogle Scholar
  167. 167.
    Carp H, Janoff A: Potential mediator of inflammation phagocytic-derived oxidants suppress the elastase-inhibitory capacity of alphaj-proteinase inhibitor in vitro. J Clin Invest 66: 987–995, 1980.PubMedGoogle Scholar
  168. 168.
    Farber CM, Liebes LF, Kanganis DN, et al: Human B lymphocytes show greater susceptibility to H202 toxicity than T lymphocytes. J Immunol 132: 2543–2546, 1984.PubMedGoogle Scholar
  169. 169.
    Seaman WE, Gindhart TD, Blackman MA, et al: Natural killing of tumor cells by human pe-ripheral blood cells. J Clin Invest 67: 1324–1333, 1981.PubMedGoogle Scholar
  170. 170.
    Urbaniak SJ: ADCC (K-cell) lysis of human erythrocytes sensitized with rhesus alloantibodies. Br J Haematol 42: 315–328, 1979.PubMedGoogle Scholar
  171. 171.
    Ramos OF, Mascucci M, Klein E: Modulation of human blood lymphocyte cytotoxicity for the phorbol ester tumor promoter P(Bu)2: Increase of target binding, impairment of effector recycling and activation of lytic potential which is independent of IL-2. Cell Immunol 91: 178–192, 1985.PubMedGoogle Scholar
  172. 172.
    Kay HD, Smith DL: Regulation of human lymphocyte-mediated natural killer (NK) cell activity. J Immunol 130: 475–483, 1983.PubMedGoogle Scholar
  173. 173.
    Dallegri F, Patrone F, Frumento G: Down-regulation of K cell activity by neutrophils. Blood 65: 571–577, 1985.PubMedGoogle Scholar
  174. 174.
    Nissen-Meyer J, Kildahl-Andersen O, Austgulen R: Human monocyte-released cytotoxic factor: Effect on various cellular functions, and dependency of cytolysis on various metabolic processes. J Leukocyte Biol 40: 121–132, 1986.PubMedGoogle Scholar
  175. 175.
    Niwa Y, Sakane T, Shingu, M, et al: Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes—A possible role of increased oxygen radicals generated by the neutrophils. J Clin Immunol 3: 228–240, 1983.PubMedGoogle Scholar
  176. 176.
    de Vries JE, Caviles AP Jr, Bont WS, et al: The role of monocytes in human lymphocyte activation by mitogens. J Immunol 122: 1099–1107, 1979.PubMedGoogle Scholar
  177. 177.
    Lause DB: Suppressed lymphocyte reactivity following lymphocyte interaction with macrophages. J Reticuloendothel Soc 26: 775–786, 1979.PubMedGoogle Scholar
  178. 178.
    Novogrodsky A, Patya M, Rubin A, et al: Inhibition of B-adrenergic stimulation of lymphocyte adenylate cyclase by phorbol myristate acetate is mediated by activated macrophages. Biochem Biophys Res Commun 104: 389–393, 1982.PubMedGoogle Scholar
  179. 179.
    Metzger Z, Hoffeld JT, Oppenheim JJ: Macrophage-mediated suppression. J Immunol 124: 983–988, 1980.PubMedGoogle Scholar
  180. 180.
    Fisher RI, Bostick-Bruton F: Depressed T cell proliferative responses in Hodgkin’s disease: Role of monocyte-mediated suppression via prostaglandins and hydrogen peroxide. J Immunol 129: 1770–1774, 1982.PubMedGoogle Scholar
  181. 181.
    Bomalaski JS, Clark MA, Douglas SD: Enhanced Phospholipase A2 and C activities of peripheral blood polymorphonuclear leukocytes from patients with rheumatoid arthritis. J Leukocyte Biol 38: 649–654, 1985.PubMedGoogle Scholar
  182. 182.
    Randazzo B, Hirschberg T, Hirschberg H: Cytotoxic effects of activated human monocytes and lymphocytes to anti-D-treated human erythrocytes in vitro. Scand J Immunol 9: 351–358, 1979.PubMedGoogle Scholar
  183. 183.
    Nyholm RE, Currie GA: Monocytes and macrophages in malignant melanoma in Lysis of anti-body-coated human erythrocytes as an assay of monocyte function. Br J Cancer 37: 337–344, 1978.PubMedGoogle Scholar
  184. 184.
    Bass DA, Olbrantz P, Szejda P, et al: Subpopulations of neutrophils with increased oxidative product formation in blood of patients with infection. J Immunol 136: 860–866, 1984.Google Scholar
  185. 185.
    Bass DA, Grover WH, Lewis JC, et al: Comparison of human eosinophils from normals and patients with eosinophilia. J Clin Invest 66: 1265–1273, 1980.PubMedGoogle Scholar
  186. 186.
    Kitahara M, Eyre HJ, Hill HR: Monocyte functional and metabolic activity in malignant and inflammatory diseases. J Lab Clin Med 93: 472–479, 1979.PubMedGoogle Scholar
  187. 187.
    Deshazo RD, Ewel C, Londono S, et al: Evidence for the involvement of monocyte-derived toxic oxygen metabolites in the lymphocyte dysfunction of Hodgkin’s disease. Clin Exp Immunol 46: 313–320, 1981.PubMedGoogle Scholar
  188. 188.
    Nagai H, Fisher RI, Cossman J, et al: Decreased expression of Class II major histocompatibility antigens on monocytes from patients with Hodgkin’s disease. J Leukocyte Biol 39: 313–321, 1986.PubMedGoogle Scholar
  189. 189.
    Metzger Z, Hoffeld JT, Oppenheim JJ: Regulation by PGE2 of the production of oxygen intermedi-ates by LPS-activated macrophages. J Immunol 127: 1109–1113, 1981.PubMedGoogle Scholar
  190. 190.
    Bray RA, Brahmi Z: Role of lipoxygenation in human natural killer cell activation. J Immunol 136: 1783–1798, 1986.PubMedGoogle Scholar
  191. 191.
    Singh D, Greenwald J, Bianchine J, et al: Evidence for the generation of hydroxyj radical during arachidonic acid metabolism by human platelets. Am J Hematol 11: 233–240, 1981.PubMedGoogle Scholar
  192. 192.
    Harrel RA, Cianciolo CJ, Copeland TD: Suppression of the respiratory burst of human monocytes by a synthetic peptide homologous to envelope proteins of human and animal retroviruses. J Immunol 186: 3517–3528, 1986.Google Scholar
  193. 193.
    Cianciolo GJ, Copeland TD, Oroszlan S, et al: Inhibition of lymphocyte proliferation by a synthet-ic peptide homologous to retroviral envelope proteins. Science 230: 453–455, 1985.PubMedGoogle Scholar
  194. 194.
    Rhodes J, Bishop M, Benfield J: Tumor Surveillance: How tumors may resist macrophage-mediated host defense. Science 203: 179–182, 1979.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Arthur L. SagoneJr.
    • 1
  1. 1.Department of Medicine and Pharmacology, Division of Hematology and OncologyOhio State University, College of MedicineColumbusUSA

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