Biochemistry of Lymphokine Action on Macrophages

Modulation of Macrophage Superoxide Production by Lymphokine
  • Maya Freund
  • Edgar Pick
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Macrophages (MPs) respond to certain membrane stimulants by a sequence of biochemical reactions known as the oxidative burst (Johnston, 1978). The primary event in the sequence is the reduction of molecular oxygen to superoxide (O 2 - ) catalyzed by a membrane-associated NADPH oxidase. Part of O 2 - is further converted to hydrogen peroxide (H2O2) by enzymatic or spontaneous dismutation.


Migration Inhibitory Factor Phorbol Myristate Acetate Oxidative Burst Wheat Germ Agglutinin Peritoneal Exudate Cell 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alföldy, P., and Lemmel, E. M., 1979, Reduction of nitroblue tetrazolium for functional evaluation of activated macrophages in the cell-mediated immune reaction, Clin. Immunol. Immunopathol. 12:263–270.PubMedCrossRefGoogle Scholar
  2. Block, B., Bernheim, H.A., Wenc, K., and Jaksche, H., 1980, Purified human MIF: Effect on oxidative metabolism and surface architecture of effector cells, in: Biochemical Characterization of Lymphognes (A. L. De Weck, F. Kristensen, and M. Landy, eds.), pp. 79–83, Academic Press, New York.Google Scholar
  3. Boraschi, D., Ghezzi, P., Salmona, M., and Tagliabue, A., 1982, IFN-β-induced reduction of superoxide anion generation by macrophages, Immunology 45:621–628.PubMedGoogle Scholar
  4. Bromberg, Y., and Pick, E., 1983, Unsaturated fatty acids as second messengers of superoxide generation by macrophages, Cell. Immunol. 79:240–252.PubMedCrossRefGoogle Scholar
  5. Bryant, S. M., Lynch, R. E., and Hill, H. R., 1982, Kinetic analysis of superoxide anion production by activated and resident murine peritoneal macrophages, Cell. Immunol. 69:46–58.PubMedCrossRefGoogle Scholar
  6. Fowles, R. E., Fajardo, I. M., Leibowitch, J. L., and David, J. R., 1973, The enhancement of macrophage bacteriostasis by products of activated lymphocytes, J. Exp. Med. 138:952–964.PubMedCrossRefGoogle Scholar
  7. Gately, C. L., and Oppenheim, J. J., 1982, Activation of macrophages by lymphokines: A factor which induces hydrogen peroxide production by macrophage-like cell lines, Fed. Proc. 41:768.Google Scholar
  8. Johnston, R. B., 1978, Oxygen metabolism and the microbicidal activity of macrophages, Fed. Proc. 37:2759–2764.PubMedGoogle Scholar
  9. Johnston, R. B., 1981, Enhancement of phagocytosis-associated oxidative metabolism as a manifestation of macrophage activation, Lymphokines 3:33–56.Google Scholar
  10. Krueger, G.G., Ogden, B. E., and Weston, W. L., 1976, In vitro quantitation of cell mediated immunity in guinea pigs by macrophage reduction of nitroblue tetrazolium, Clin. Exp. Immunol. 23:517–524.PubMedGoogle Scholar
  11. Lowry, O. H., Rosebrough, N., Farr, A. L., and Randall, R. J., 1951, Protein measurement with the Folin phenol reagent, J. Biol. Chem. 193:265–275.PubMedGoogle Scholar
  12. Manheimer, S., and Pick, E., 1973, The mechanism of action of soluble lymphocytic mediators. I. A pulse exposure test for the measurement of macrophage migration inhibitory factor, Immunology 24:1027–1034.PubMedGoogle Scholar
  13. Murray, H. W., 1981, 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
  14. 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
  15. Nakagawara, A., de Santis, N., 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
  16. Nathan, C. F., Karnovsky, M. L., and David, J. R., 1971, Alterations of macrophage functions by mediators from lymphocytes, J. Exp. Med. 133:1356–1376.PubMedCrossRefGoogle Scholar
  17. Nathan, C. F., Nogueira, N., Juangbhanich, C., Ellis, J., and Cohn, Z., 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.PubMedCrossRefGoogle Scholar
  18. Pabst, M. J., and Johnston, R. B., 1980, Increased production of superoxide anion by macrophages exposed in vitro to muramyl dipeptide or lipopolysaccharide, J. Exp. Med. 151:101–114.PubMedCrossRefGoogle Scholar
  19. Pabst, M. J., Hedegaard, H. B., and Johnston, R. B., 1982, Cultured human monocytes require exposure to bacterial products to maintain an optimal oxygen radical response, J. Immunol. 128:123–128.PubMedGoogle Scholar
  20. Pick, E., and Freund, M., 1984, Biochemical mechanisms in macrophage activation by lymphokines: Intracellular peroxide production by lymphokine-treated macrophages, in: Progress in Immunology, V (T. Tada, ed.), Academic Press, New York, in press.Google Scholar
  21. Pick, E., and Keisari, Y., 1981, Superoxide anion and hydrogen peroxide production by chemically elicited peritoneal macrophages—Induction by multiple nonphagocytic stimuli, Cell. Immunol. 59:301–318.PubMedCrossRefGoogle Scholar
  22. Pick, E., and Kotkes, P., 1977, A simple method for the production of migration inhibitory factor by concanavalin A-stimulated lymphocytes, J. Immunol. Methods 14:141–146.PubMedCrossRefGoogle Scholar
  23. Pick, E., and Mizel, D., 1981, Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader, J. Immunol. Methods 46:211–226.PubMedCrossRefGoogle Scholar
  24. Seim, S., 1982, Production of reactive oxygen species and chemiluminescence by human monocytes during differentiation and lymphokine activation in vitro, Acta Pathol. Microbiol. Immunol. Scand. Sect. C 90:179–185.Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Maya Freund
    • 1
  • Edgar Pick
    • 1
  1. 1.Laboratory of Immunopharmacology, Department of Human Microbiology, Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael

Personalised recommendations