Macrophage Activation: Enhanced Oxidative and Antiprotozoal Activity

  • Henry W. Murray
Part of the Contemporary Topics in Immunobiology book series (CTI, volume 13)


Although only one of the array of secretory properties displayed by activated macrophages, the capacity to generate increased amounts of reactive oxygen intermediates is a consistent biochemical marker of activation with clearly relevant biologic effects (Nathan et al., 1980). Thus, the ability to secrete high levels of superoxide anion (O2 ) and hydrogen peroxide (H2O2) appears to contribute in an important way to the capacity to exert enhanced antimicrobial activity—a particularly key expression of the activated state (North, 1979). Current evidence suggests, for example, that (1) those mononuclear phagocytes that are capable of killing intracellular pathogens such as protozoa, fungi, and mycobacteria depend in large measure on this oxygen-dependent mechanism (Haidaris and Bonventre, 1982; Murray et al., 1979; Murray and Cohn, 1980; Murray, 1981a, 1982b; Nathan et al., 1979; Sasada and Johnston, 1980; Walker and Lowrie, 1981), and (2) secreted O2 and H2O2 may also be active against certain extracellular microbial targets too large to be ingested (Diamond et al., 1982; Kazura et al., 1981).


Peritoneal Macrophage Phorbol Myristate Acetate Chronic Granulomatous Disease Phorbol Myristate Acetate Respiratory Burst Activity 
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  1. Anderson, S. E., Bautista, S., and Remington, J. S., 1976, Induction of resistance to Toxoplasma gondii in human macrophages by soluble lymphocyte products, J. Immunol. 117: 381–387.PubMedGoogle Scholar
  2. Badway, J. A., and Karnovsky, M. L., 1980, Active oxygen species and the functions of phagocytic leukocytes, Annu. Rev. Biochem. 49: 595–622.Google Scholar
  3. Borges, J. S., and Johnson, W. D., 1975, Inhibition of multiplication of Toxoplasma gondii by human monocytes exposed to T-lymphocyte products, J. Exp. Med. 141: 438–496.CrossRefGoogle Scholar
  4. Byrne, G. I., and Favbion, C., 1982, Lymphokine-mediated microbistatic mechanisms re-strict Chlamydia psittaci growth in macrophages, J. Immunol. 128: 469–474.PubMedGoogle Scholar
  5. Diamond, R. D., Haudenschild, C. C., and Erickson, N. F., 1982, Monocyte-mediated damage to Rhizopus oryzae hyphae in vitro, Infect. Immun. 38: 292–297.PubMedGoogle Scholar
  6. Haidaris, C. G., and Bonventre, P. F., 1982, A role for oxygen-dependent mechanisms in killing of Leishmania donovani tissue forms by activated macrophages, J. Immunol. 129: 350–355.Google Scholar
  7. Johnston, R. B., Godzik, C. A., and Cohn, Z. A., 1978, Increased superoxide anion production by immunologically activated and chemically elicited macrophages, J. Exp. Med. 148: 115–126.PubMedCrossRefGoogle Scholar
  8. Kazura, J. W., Fanning, M. M., Blumes, J. T., and Mahmoud, A. A., 1981, Role of cell-generated H2O2 in granulocyte-mediated killing of schistosomula of Schistosoma mansoni, J. Clin. Invest. 67: 93–102.PubMedCrossRefGoogle Scholar
  9. Klebanoff, S. J., 1980, Oxygen metabolism and the toxic properties of phagocytes, Ann. Intern. Med. 93: 480–489.PubMedCrossRefGoogle Scholar
  10. Locksley, R. M., Wilson, C. B., and Klebanoff, S. J., 1982, Role for endogenous and acquired peroxidase in the toxoplasmacidal activity of murine and human mononuclear phagocytes, J. Clin. Invest. 69: 1099–1111.PubMedCrossRefGoogle Scholar
  11. Murray, H. W., 1981a, Susceptibility of Leishmania to oxygen intermediates and killing by normal macrophages, J. Exp. Med. 153: 1302–1315.PubMedCrossRefGoogle Scholar
  12. Murray, H. W., 1981b, Interaction of Leishmania with a macrophage cell line. Correlation between intracellular killing and the generation of oxygen intermediates, J. Exp. Med. 153: 1690–1695.PubMedCrossRefGoogle Scholar
  13. Murray, H. W., 1982a, Cell-mediated immune response in experimental visceral leishmaniasis. II. Oxygen-dependent killing of intracellular Leishmania donovani amastigotes, J. Immunol. 129: 351–357.PubMedGoogle Scholar
  14. Murray, H. W., 1982b, Pretreatment with phorbol myristate acetate inhibits macrophage activity against intracellular protozoa, J. Reticuloendothel. Soc. 37: 479–487.Google Scholar
  15. Murray, H. W., and Cartelli, D. M., 1983, Killing of intracellular Leishmania donovani by human mononuclear phagocytes: Evidence for oxygen-dependent and -independent leishmanicidal activity, J. Clin. Invest. 72: 32–41.PubMedCrossRefGoogle Scholar
  16. Murray, H. W., and Cohn, Z. A., 1979, Macrophage oxygen-dependent antimicrobial activity. I. Susceptibility of Toxoplasma gondii to oxygen intermediates, J. Exp. Med. 150: 983–979.Google Scholar
  17. Murray, H. W., and Cohn, Z. A., 1980, Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation, J. Exp. Med. 152: 1596–1609.PubMedCrossRefGoogle Scholar
  18. Murray, H. W., Juangbhanich, C. W., Nathan, C. F., and Cohn, Z. A., 1979, Macrophage oxygen-dependent antimicrobial activity. II. The role of oxygen intermediates, J. Exp. Med. 150: 950–864.PubMedCrossRefGoogle Scholar
  19. Murray, H. W., Nathan, C. F., and Cohn, Z. A., 1980, Macrophage oxygen-dependent antimicrobial activity. IV. The role of endogenous scavengers of oxygen intermediates, J. Exp. Med. 152: 1610–1624.PubMedCrossRefGoogle Scholar
  20. Murray, H. W., Masur, H., and Keithly, J. S., 1982, Cell-mediated immune response in experimental visceral leishmaniasis. I. Correlation between resistance to Leishmania donovani and lymphokine-generating capacity, J. Immunol. 129: 344–350.Google Scholar
  21. Murray, H. W., Byrne, G. 1., Rothermel, C. D., and Cartelli, D. M., 1983, Lymphokine enhances oxygen-dependent activity against intracellular pathogens, J. Exp. Med. 158: 234–235.Google Scholar
  22. Nacy, C. A., Meltzer, M. S., Leonard, E. J., and Wyler, D. J., 1981, Intracellular replication and lymphokine-induced destruction of Leishmania tropico in C3H/Hen mouse macrophages, J. Immunol. 127: 2381–2386.PubMedGoogle Scholar
  23. Nakagawara, A., Nathan, C. F., and Cohen, Z. A., 1981, Hydrogen peroxide metabolism in human monocytes during differentiation in vitro, J. Clin. Invest. 68: 1243–1252.PubMedCrossRefGoogle Scholar
  24. Nakagawara, A., DeSantis, N. M., Nogueira, N., and Nathan, C. F., 1982, Lymphokines enhance the capacity of human monocytes to secrete reactive oxygen intermediates, J. Clin. Invest. 70: 1042–1048.PubMedCrossRefGoogle Scholar
  25. Nathan, C. F., and Root, R. K., 1977, Hydrogen peroxide release from mouse peritoneal macrophages, J. Exp. Med. 146: 1648–1662.PubMedCrossRefGoogle Scholar
  26. Nathan, C. F., Nogueira, N., Juangbhanich, C., Ellis,J., and Cohn, Z. A., 1979, Activation of macrophages in vivo and in vitro. Correlation between hydrogen peroxide release and killing of Trypanosoma cruzi, J. Exp. Med. 149: 1056–1068.Google Scholar
  27. Nathan, C. F., Murray, H. W., and Cohn, Z. A., 1980, The macrophage as an effector cell, N. Engl. J. Med. 303: 622–626.PubMedCrossRefGoogle Scholar
  28. North, R. J., 1978, The concept of the activated macrophage, J. Immunol. 121: 806–808.PubMedGoogle Scholar
  29. Pabst, M. J., Hedegaard, H. B., and Johnston, R. B. 1982, Cultured human monocytes re-quire exposure to bacterial products to maintain an optimal oxygen radical response,J. Immunol. 128:123–128.Google Scholar
  30. Pearson, R. D., Romito, R, Symes, P. H., and Harcus, J. L., 1981, Interaction of LeishmaniaMacrophage Oxidative and Antiprotozoal Activity 115 donovani promastigotes with human monocyte-derived macrophages: Parasite entry, intracellular survival, and multiplication, Infect. Immun. 32:1249–1253.Google Scholar
  31. Rosen, H., and Klebanoff, S. J., 1979, Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte, J. Exp. Med. 149: 27–40.PubMedCrossRefGoogle Scholar
  32. Rothermel, C. D., Byrne, G. I., and Murray, H. W., 1982, Growth of Chlamydia psittaci in human monocytes (abstract), in: 22nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Miami, 1982, No. 36.Google Scholar
  33. Sasada, M., and Johnston, R. B., 1980, Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing of Candida by macrophages, J. Exp. Med. 152: 85–99.PubMedCrossRefGoogle Scholar
  34. Szuro-Sudol, A., and Nathan, C. F., 1982, Suppression of macrophage oxidative metab-olism by products of malignant and non-malignant cells, J. Exp. Med. 156: 945–961.PubMedCrossRefGoogle Scholar
  35. Szuro-Sudol, A., Murray, H. W., and Nathan, C. F., 1983, Supression of macrophage anti-microbial activity by a tumor cell product, J. Immunol. 131: 384–385.PubMedGoogle Scholar
  36. Walker, L., and Lowrie, D. B., 1981, Killing of Mycobacterium microti by immunologically activated macrophages, Nature 293: 69–70.PubMedCrossRefGoogle Scholar
  37. Wilson, C. B., Tsai, V., and Remington, J. S., 1980, Failure to trigger the oxidative burst by normal macrophages. Possible mechanism for survival of intracellular pathogens, J. Exp. Med. 151: 328–346.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Henry W. Murray
    • 1
  1. 1.Department of MedicineThe Cornell University Medical CollegeNew YorkUSA

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