Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1990 May;58(5):1296–1300. doi: 10.1128/iai.58.5.1296-1300.1990

In vivo activation of macrophage oxidative burst activity by cytokines and amphotericin B.

J E Wolf 1, S E Massof 1
PMCID: PMC258623  PMID: 2157668

Abstract

Alterations in macrophage oxidative burst activity following in vivo administration of recombinant murine gamma interferon (IFN-gamma), recombinant murine tumor necrosis factor alpha, and the antifungal antibiotic amphotericin B were investigated. Mice were given intraperitoneal injections of these agents alone and in combination, and the oxidative responses of their resident peritoneal macrophages to challenge with Histoplasma capsulatum or zymosan particles were measured 1 to 5 days later. Various degrees of enhanced oxidative burst activity were achieved following treatment with each agent. However, a synergistic response was observed only when mice were treated with the combination of recombinant murine IFN-gamma and amphotericin B. These results not only confirm the dual role of amphotericin as an antifungal agent and as an immunomodulator but also suggest that IFN-gamma may serve as a useful adjunct in the treatment of intracellular fungal infections.

Full text

PDF
1296

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beaman L., Benjamini E., Pappagianis D. Activation of macrophages by lymphokines: enhancement of phagosome-lysosome fusion and killing of Coccidioides immitis. Infect Immun. 1983 Mar;39(3):1201–1207. doi: 10.1128/iai.39.3.1201-1207.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beaman L. Fungicidal activation of murine macrophages by recombinant gamma interferon. Infect Immun. 1987 Dec;55(12):2951–2955. doi: 10.1128/iai.55.12.2951-2955.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Belosevic M., Davis C. E., Meltzer M. S., Nacy C. A. Regulation of activated macrophage antimicrobial activities. Identification of lymphokines that cooperate with IFN-gamma for induction of resistance to infection. J Immunol. 1988 Aug 1;141(3):890–896. [PubMed] [Google Scholar]
  4. Black C. M., Catterall J. R., Remington J. S. In vivo and in vitro activation of alveolar macrophages by recombinant interferon-gamma. J Immunol. 1987 Jan 15;138(2):491–495. [PubMed] [Google Scholar]
  5. Brummer E., Morrison C. J., Stevens D. A. Recombinant and natural gamma-interferon activation of macrophages in vitro: different dose requirements for induction of killing activity against phagocytizable and nonphagocytizable fungi. Infect Immun. 1985 Sep;49(3):724–730. doi: 10.1128/iai.49.3.724-730.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brummer E., Stevens D. A. Fungicidal mechanisms of activated macrophages: evidence for nonoxidative mechanisms for killing of Blastomyces dermatitidis. Infect Immun. 1987 Dec;55(12):3221–3224. doi: 10.1128/iai.55.12.3221-3224.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Catterall J. R., Black C. M., Leventhal J. P., Rizk N. W., Wachtel J. S., Remington J. S. Nonoxidative microbicidal activity in normal human alveolar and peritoneal macrophages. Infect Immun. 1987 Jul;55(7):1635–1640. doi: 10.1128/iai.55.7.1635-1640.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chia J. K., Pollack M. Amphotericin B induces tumor necrosis factor production by murine macrophages. J Infect Dis. 1989 Jan;159(1):113–116. doi: 10.1093/infdis/159.1.113. [DOI] [PubMed] [Google Scholar]
  9. Denis M., Chadee K. Cytokine activation of murine macrophages for in vitro killing of Entamoeba histolytica trophozoites. Infect Immun. 1989 Jun;57(6):1750–1756. doi: 10.1128/iai.57.6.1750-1756.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eissenberg L. G., Goldman W. E. Histoplasma capsulatum fails to trigger release of superoxide from macrophages. Infect Immun. 1987 Jan;55(1):29–34. doi: 10.1128/iai.55.1.29-34.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Esparza I., Männel D., Ruppel A., Falk W., Krammer P. H. Interferon gamma and lymphotoxin or tumor necrosis factor act synergistically to induce macrophage killing of tumor cells and schistosomula of Schistosoma mansoni. J Exp Med. 1987 Aug 1;166(2):589–594. doi: 10.1084/jem.166.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Flesch I. E., Schwamberger G., Kaufmann S. H. Fungicidal activity of IFN-gamma-activated macrophages. Extracellular killing of Cryptococcus neoformans. J Immunol. 1989 May 1;142(9):3219–3224. [PubMed] [Google Scholar]
  13. Hamilton-Miller J. M. Fungal sterols and the mode of action of the polyene antibiotics. Adv Appl Microbiol. 1974;17(0):109–134. doi: 10.1016/s0065-2164(08)70556-2. [DOI] [PubMed] [Google Scholar]
  14. Heidenreich S., Weyers M., Gong J. H., Sprenger H., Nain M., Gemsa D. Potentiation of lymphokine-induced macrophage activation by tumor necrosis factor-alpha. J Immunol. 1988 Mar 1;140(5):1511–1518. [PubMed] [Google Scholar]
  15. Kaushansky K., Broudy V. C., Harlan J. M., Adamson J. W. Tumor necrosis factor-alpha and tumor necrosis factor-beta (lymphotoxin) stimulate the production of granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and IL-1 in vivo. J Immunol. 1988 Nov 15;141(10):3410–3415. [PubMed] [Google Scholar]
  16. Lin S. H., Medoff G., Kobayashi G. S. Effects of amphotericin B on macrophages and their precursor cells. Antimicrob Agents Chemother. 1977 Jan;11(1):154–160. doi: 10.1128/aac.11.1.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mauël J., Buchmüller-Rouiller Y. Effect of lipopolysaccharide on intracellular killing of Leishmania enriettii and correlation with macrophage oxidative metabolism. Eur J Immunol. 1987 Feb;17(2):203–208. doi: 10.1002/eji.1830170209. [DOI] [PubMed] [Google Scholar]
  18. Medoff G., Brajtburg J., Kobayashi G. S., Bolard J. Antifungal agents useful in therapy of systemic fungal infections. Annu Rev Pharmacol Toxicol. 1983;23:303–330. doi: 10.1146/annurev.pa.23.040183.001511. [DOI] [PubMed] [Google Scholar]
  19. Murray H. W., Byrne G. I., Rothermel C. D., Cartelli D. M. Lymphokine enhances oxygen-independent activity against intracellular pathogens. J Exp Med. 1983 Jul 1;158(1):234–239. doi: 10.1084/jem.158.1.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Murray H. W., Cohn Z. A. Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation. J Exp Med. 1980 Dec 1;152(6):1596–1609. doi: 10.1084/jem.152.6.1596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Murray H. W. Interferon-gamma, the activated macrophage, and host defense against microbial challenge. Ann Intern Med. 1988 Apr;108(4):595–608. doi: 10.7326/0003-4819-108-4-595. [DOI] [PubMed] [Google Scholar]
  22. Murray H. W., Spitalny G. L., Nathan C. F. Activation of mouse peritoneal macrophages in vitro and in vivo by interferon-gamma. J Immunol. 1985 Mar;134(3):1619–1622. [PubMed] [Google Scholar]
  23. Nacy C. A., Fortier A. H., Meltzer M. S., Buchmeier N. A., Schreiber R. D. Macrophage activation to kill Leishmania major: activation of macrophages for intracellular destruction of amastigotes can be induced by both recombinant interferon-gamma and non-interferon lymphokines. J Immunol. 1985 Nov;135(5):3505–3511. [PubMed] [Google Scholar]
  24. Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pabst M. J., Johnston R. B., Jr Increased production of superoxide anion by macrophages exposed in vitro to muramyl dipeptide or lipopolysaccharide. J Exp Med. 1980 Jan 1;151(1):101–114. doi: 10.1084/jem.151.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pace J. L., Russell S. W., Torres B. A., Johnson H. M., Gray P. W. Recombinant mouse gamma interferon induces the priming step in macrophage activation for tumor cell killing. J Immunol. 1983 May;130(5):2011–2013. [PubMed] [Google Scholar]
  27. Patterson-Delafield J., Martinez R. J., Lehrer R. I. Microbicidal cationic proteins in rabbit alveolar macrophages: a potential host defense mechanism. Infect Immun. 1980 Oct;30(1):180–192. doi: 10.1128/iai.30.1.180-192.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Perfect J. R., Granger D. L., Durack D. T. Effects of antifungal agents and gamma interferon on macrophage cytotoxicity for fungi and tumor cells. J Infect Dis. 1987 Aug;156(2):316–323. doi: 10.1093/infdis/156.2.316. [DOI] [PubMed] [Google Scholar]
  29. Philip R., Epstein L. B. Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1. Nature. 1986 Sep 4;323(6083):86–89. doi: 10.1038/323086a0. [DOI] [PubMed] [Google Scholar]
  30. Segal G. P., Lehrer R. I., Selsted M. E. In vitro effect of phagocyte cationic peptides on Coccidioides immitis. J Infect Dis. 1985 May;151(5):890–894. doi: 10.1093/infdis/151.5.890. [DOI] [PubMed] [Google Scholar]
  31. Sokol-Anderson M. L., Brajtburg J., Medoff G. Amphotericin B-induced oxidative damage and killing of Candida albicans. J Infect Dis. 1986 Jul;154(1):76–83. doi: 10.1093/infdis/154.1.76. [DOI] [PubMed] [Google Scholar]
  32. Tomazic V. J., Farha M., Loftus A., Elias E. G. Anti-tumor activity of recombinant tumor necrosis factor on mouse fibrosarcoma in vivo and in vitro. J Immunol. 1988 Jun 1;140(11):4056–4061. [PubMed] [Google Scholar]
  33. Wing E. J., Ampel N. M., Waheed A., Shadduck R. K. Macrophage colony-stimulating factor (M-CSF) enhances the capacity of murine macrophages to secrete oxygen reduction products. J Immunol. 1985 Sep;135(3):2052–2056. [PubMed] [Google Scholar]
  34. Wolf J. E., Abegg A. L., Travis S. J., Kobayashi G. S., Little J. R. Effects of Histoplasma capsulatum on murine macrophage functions: inhibition of macrophage priming, oxidative burst, and antifungal activities. Infect Immun. 1989 Feb;57(2):513–519. doi: 10.1128/iai.57.2.513-519.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wolf J. E., Kerchberger V., Kobayashi G. S., Little J. R. Modulation of the macrophage oxidative burst by Histoplasma capsulatum. J Immunol. 1987 Jan 15;138(2):582–586. [PubMed] [Google Scholar]
  36. Wu-Hsieh B. A., Howard D. H. Inhibition of the intracellular growth of Histoplasma capsulatum by recombinant murine gamma interferon. Infect Immun. 1987 Apr;55(4):1014–1016. doi: 10.1128/iai.55.4.1014-1016.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES