Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1987 Dec;70(3):520–528.

Activation of pulmonary macrophages for fungicidal activity by gamma-interferon or lymphokines.

E Brummer 1, D A Stevens 1
PMCID: PMC1542173  PMID: 3124995

Abstract

The ability of murine recombinant gamma interferon (IFN) or lymphokines to enhance the fungicidal activity of murine pulmonary macrophages (PuM) was studied in in vitro. PuM monolayers were incubated overnight with IFN, lymph node cells (LNC) plus concanavalin A, supernatants from Con A stimulated LNC or spleen cell cultures (Con A Sup), or tissue culture medium (TCM) +/- Con A (5 micrograms/ml) or +/- lipopolysaccharide (LPS, 10 ng to 10 micrograms/ml). After treatment, culture fluids were removed and PuM were challenged for 4 h with the yeast-form Blastomyces dermatitidis or 2 h with Candida albicans. Inoculum colony forming units (CFU) of B. dermatitidis were significantly reduced by PuM treated with 1000 U/ml of IFN (25 +/- 3%), Con A Sup (25 +/- 3%) or LNC plus Con A (37-44%), but not by TCM, ConA or LPS. Candida albicans was killed by PuM treated with Con A Sup (33 +/- 8%) or LNC plus Con A (30-43%), but not by TCM, Con A, or LPS, and the activity of Con A Sup was neutralized by anti-IFN antibody. Candida albicans was not significantly killed by PuM treated with IFN doses ranging from 1 to 10(5) U/ml; nor did addition of LPS to IFN, or prolonged (3 day) treatment with IFN, result in significant killing of C. albicans by PuM. However, IFN (100 U/ml) could activate resident peritoneal macrophages for significant candidacidal activity (63%). These data indicate that PuM can be activated for fungicidal activity, and that PuM differ from resident peritoneal macrophages with regard to induction of candidacidal activity by recombinant gamma-IFN.

Full text

PDF

Selected References

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

  1. Akagawa K. S., Tokunaga T. Lack of binding of bacterial lipopolysaccharide to mouse lung macrophages and restoration of binding by gamma interferon. J Exp Med. 1985 Nov 1;162(5):1444–1459. doi: 10.1084/jem.162.5.1444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beaman L., Holmberg C. A. In vitro response of alveolar macrophages to infection with Coccidioides immitis. Infect Immun. 1980 May;28(2):594–600. doi: 10.1128/iai.28.2.594-600.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bordignon C., Avallone R., Peri G., Polentarutti N., Mangioni C., Mantovani A. Cytotoxicity on tumour cells of human mononuclear phagocytes: defective tumoricidal capacity of alveolar macrophages. Clin Exp Immunol. 1980 Aug;41(2):336–342. [PMC free article] [PubMed] [Google Scholar]
  4. Brass C., Volkmann C. M., Klein H. P., Halde C. J., Archibald R. W., Stevens D. A. Pathogen factors and host factors in murine pulmonary blastomycosis. Mycopathologia. 1982 Jun 18;78(3):129–140. doi: 10.1007/BF00466066. [DOI] [PubMed] [Google Scholar]
  5. Brass C., Volkmann C. M., Philpott D. E., Klein H. P., Halde C. J., Stevens D. A. Spontaneous mutant of Blastomyces dermatitidis attenuated in virulence for mice. Sabouraudia. 1982 Jun;20(2):145–158. [PubMed] [Google Scholar]
  6. 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]
  7. COHN Z. A., WIENER E. THE PARTICULATE HYDROLASES OF MACROPHAGES. I. COMPARATIVE ENZYMOLOGY, ISOLATION, AND PROPERTIES. J Exp Med. 1963 Dec 1;118:991–1008. doi: 10.1084/jem.118.6.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis-Scibienski C., Beaman B. L. Interaction of alveolar macrophages with Nocardia asteroides: immunological enhancement of phagocytosis, phagosome-lysosome fusion, and microbicidal activity. Infect Immun. 1980 Nov;30(2):578–587. doi: 10.1128/iai.30.2.578-587.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fromtling R. A., Shadomy H. J. Immunity in cryptococcosis: an overview. Mycopathologia. 1982 Mar 19;77(3):183–190. doi: 10.1007/BF00518804. [DOI] [PubMed] [Google Scholar]
  10. Gomez J., Pohajdak B., O'Neill S., Wilkins J., Greenberg A. H. Activation of rat and human alveolar macrophage intracellular microbicidal activity by a preformed LGL cytokine. J Immunol. 1985 Aug;135(2):1194–1200. [PubMed] [Google Scholar]
  11. Hamann U., Krammer P. H. Activation of macrophage tumor cytotoxicity by the synergism of two T cell-derived lymphokines: immune interferon (IFN-gamma) and macrophage cytotoxicity-inducing factor 2 (MCIF2). Eur J Immunol. 1985 Jan;15(1):18–24. doi: 10.1002/eji.1830150105. [DOI] [PubMed] [Google Scholar]
  12. Hearst J. E., Warr G. A., Jakab G. J. Characterization of murine lung and peritoneal macrophages. J Reticuloendothel Soc. 1980 May;27(5):443–454. [PubMed] [Google Scholar]
  13. Jakab G. J. Factors influencing the immune enhancement of intrapulmonary bactericidal mechanisms. Infect Immun. 1976 Aug;14(2):389–398. doi: 10.1128/iai.14.2.389-398.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnson J. D., Hand W. L., King N. L., Hughes C. G. Activation of alveolar macrophages after lower respiratory tract infection. J Immunol. 1975 Jul;115(1):80–84. [PubMed] [Google Scholar]
  15. Kimberlin C. L., Hariri A. R., Hempel H. O., Goodman N. L. Interactions between Histoplasma capsulatum and macrophages from normal and treated mice: comparison of the mycelial and yeast phases in alveolar and peritoneal macrophages. Infect Immun. 1981 Oct;34(1):6–10. doi: 10.1128/iai.34.1.6-10.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Leake E. S., Myrvik Q. N., Wright M. J. Phagosomal membranes of Mycobacterium bovis BCG-immune alveolar macrophages are resistant to disruption by Mycobacterium tuberculosis H37Rv. Infect Immun. 1984 Aug;45(2):443–446. doi: 10.1128/iai.45.2.443-446.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lehrer R. I., Ferrari L. G., Patterson-Delafield J., Sorrell T. Fungicidal activity of rabbit alveolar and peritoneal macrophages against Candida albicans. Infect Immun. 1980 Jun;28(3):1001–1008. doi: 10.1128/iai.28.3.1001-1008.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Leu R. W., Eddleston A. L., Hadden J. W., Good R. A. Mechanism of action of migration inhibitory factor (MIF). I. Evidence for a receptor for MIF present on the peritoneal macrophage but not on the alveolar macrophage. J Exp Med. 1972 Sep 1;136(3):589–603. doi: 10.1084/jem.136.3.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morozumi P. A., Brummer E., Stevens D. A. Protection against pulmonary blastomycosis: correlation with cellular and humoral immunity in mice after subcutaneous nonlethal infection. Infect Immun. 1982 Aug;37(2):670–678. doi: 10.1128/iai.37.2.670-678.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Murray H. W., Gellene R. A., Libby D. M., Rothermel C. D., Rubin B. Y. Activation of tissue macrophages from AIDS patients: in vitro response of AIDS alveolar macrophages to lymphokines and interferon-gamma. J Immunol. 1985 Oct;135(4):2374–2377. [PubMed] [Google Scholar]
  21. Nash T. W., Libby D. M., Horwitz M. A. Interaction between the legionnaires' disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone. J Clin Invest. 1984 Sep;74(3):771–782. doi: 10.1172/JCI111493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ryning F. W., Krahenbuhl J. L., Remington J. S. Comparison of cytotoxic and microbicidal function of bronchoalveolar and peritoneal macrophages. Immunology. 1981 Apr;42(4):513–519. [PMC free article] [PubMed] [Google Scholar]
  23. Schaffner A., Douglas H., Braude A. I., Davis C. E. Killing of Aspergillus spores depends on the anatomical source of the macrophage. Infect Immun. 1983 Dec;42(3):1109–1115. doi: 10.1128/iai.42.3.1109-1115.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Scherer S., Stevens D. A. Application of DNA typing methods to epidemiology and taxonomy of Candida species. J Clin Microbiol. 1987 Apr;25(4):675–679. doi: 10.1128/jcm.25.4.675-679.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sone S., Fidler I. J. Synergistic activation by lymphokines and muramyl dipeptide of tumoricidal properties in rat alveolar macrophages. J Immunol. 1980 Dec;125(6):2454–2460. [PubMed] [Google Scholar]
  26. Sone S., Moriguchi S., Shimizu E., Ogushi F., Tsubura E. In vitro generation of tumoricidal properties in human alveolar macrophages following interaction with endotoxin. Cancer Res. 1982 Jun;42(6):2227–2231. [PubMed] [Google Scholar]
  27. Sone S., Tsubura E. Human alveolar macrophages: potentiation of their tumoricidal activity by liposome-encapsulated muramyl dipeptide. J Immunol. 1982 Sep;129(3):1313–1317. [PubMed] [Google Scholar]
  28. Sugar A. M., Brummer E., Stevens D. A. Fungicidal activity of murine broncho-alveolar macrophages against Blastomyces dermatitidis. J Med Microbiol. 1986 Feb;21(1):7–11. doi: 10.1099/00222615-21-1-7. [DOI] [PubMed] [Google Scholar]
  29. Sugar A. M., Brummer E., Stevens D. A. Murine pulmonary macrophages: evaluation of lung lavage fluids, miniaturized monolayers, and candidacidal activity. Am Rev Respir Dis. 1983 Jan;127(1):110–112. doi: 10.1164/arrd.1983.127.1.110. [DOI] [PubMed] [Google Scholar]
  30. Sugar A. M., Chahal R. S., Brummer E., Stevens D. A. Susceptibility of Blastomyces dermatitidis strains to products of oxidative metabolism. Infect Immun. 1983 Sep;41(3):908–912. doi: 10.1128/iai.41.3.908-912.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Svedersky L. P., Benton C. V., Berger W. H., Rinderknecht E., Harkins R. N., Palladino M. A. Biological and antigenic similarities of murine interferon-gamma and macrophage-activating factor. J Exp Med. 1984 Mar 1;159(3):812–827. doi: 10.1084/jem.159.3.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Waldorf A. R., Levitz S. M., Diamond R. D. In vivo bronchoalveolar macrophage defense against Rhizopus oryzae and Aspergillus fumigatus. J Infect Dis. 1984 Nov;150(5):752–760. doi: 10.1093/infdis/150.5.752. [DOI] [PubMed] [Google Scholar]
  33. Weinberg D. S., Unanue E. R. Antigen-presenting function of alveolar macrophages: uptake and presentation of Listeria monocytogenes. J Immunol. 1981 Feb;126(2):794–799. [PubMed] [Google Scholar]
  34. Wirth J. J., Kierszenbaum F., Sonnenfeld G., Zlotnik A. Enhancing effects of gamma interferon on phagocytic cell association with and killing of Trypanosoma cruzi. Infect Immun. 1985 Jul;49(1):61–66. doi: 10.1128/iai.49.1.61-66.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES