Abstract
Four microbial and two chemically defined immunomodulating agents namely viable BCG, killed Mycobacterium butyricum, killed Lactobacillus plantarum, zymosan, tilorone, and dimethyldioctadecylammonium bromide (DDA) were studied for their effects on macrophage functions in vitro and in vivo. All agents induced a dose-dependent mortality of macrophages as determined by trypan blue exclusion. DDA and especially tilorone were rather toxic for macrophages in vitro. All agents except tilorone and DDA inhibited phagocytosis of yeast cells and uptake of acridine orange in vitro at doses which killed up to about 30% of the macrophages. DDA and tilorone had no effect at similar doses. All agents but zymosan inhibited the spreading of macrophages. No interference with the fusion of lysosomes and yeast cell-containing phagosomes could be observed. The activity of the mononuclear phagocytic system (MPS) in vivo as measured by carbon clearance was stimulated by all substances within twentyfour hours. All agents but DDA and tilorone enhanced non-specific bacterial resistance. As demostrated previously for DDA, tilorone could serve as adjuvant for induction of specific resistance to Listeria monocytogenes.
The results are discussed in relation to other data on influencing of macrophage functions and on immunomodification. It is concluded that hampered antigen destruction by local macrophage suppression attended with MPS stimulation might be a basic mechanism for adjuvanticity exerted by these agents.
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References
Armstrong, J. A. and Hart, P. D. 1971. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. — J. Exp. Med. 134: 713–740.
Arora, M. P. and Crowle, A. J. 1978. Adjuvanticity of Evans blue dye: preliminary characterization of its mechanisms and mode of application in mice. — J. Reticuloendothel. Soc. 24: 271–286.
Bianco, C., Götze, O. and Cohn, Z. A. 1978. Regulation of macrophage motility by components of the complement system. — J. Immunol. 120: 1765.
Biozzi, G., Benacerraf, B. and Halpern, B. N. 1953. Quantitative study of the granulopectic activity of the reticuloendothelial system. — II. A study of the kinetics of the granulopectic activity of the R.E.S. in relation to the dose of carbon injected. Relationship between the weight of the organs and their activity. — Brit. J. Exp. Pathol. 34: 441–457.
Biroum-Nourjasin. 1977. Listericidal activity of non-stimulated human macrophages in vitro. —Clin. Exp. Immunol. 28: 138–145.
Blanden, R. V. 1974. T-cell responses to viral and bacterial infection. — Transpl. Rev. 19: 56–88.
Bloksma, N., De Heer, E., Van Dijk, H. and Willers, J. M. N. 1979. Adjuvanticity of lactobacilli I. Differential effects of viable and killed bacteria. — Clin. Exp. Immunol. 37: 367–375.
Bloksma, N., De Reuver, M. J. and Willers, J. M. N. 1980. Influence on macrophage function as a possible basis of immunomodification by polyanions. — Ann. Immunol. (Inst. Pasteur) 131D: 255–265.
Borek, F. 1977. Adjuvants, p. 369–428. In M. Sela (ed.), The antigens. Vol. 4. —Academic Press, New York.
Crowle, A. J., Atkins, A. and May, M. J. 1977. Induction of delayed hypersensitivity to protein antigens in mice without Freund's adjuvant. — J. Allergy Clin. Immunol. 60: 14–26.
Götze, O., Bianco, C. and Cohn, Z. A. 1978. The induction of macrophage spreading by factor B of the properdin system. — J. Immunol. 120: 1776.
Hart, P. D. and Young, M. R. 1975. Interference with normal phagosome-lysosome fusion in macrophages using ingested yeast cells and suramin. — Nature (Lond.) 256: 47–49.
Kelly, M. T. 1976. Activation of guinea pig macrophages by cell walls of Mycobacterium bovis, strain BCG. — Cell. Immunol. 26: 254–263.
Nathan, C. F. and Terry, W. D. 1977. Decreased phagocytosis by peritoneal macrophages from BCG-treated mice. Induction of the phagocytic defect in normal macrophages with BCG in vitro. — Cell. Immunol. 29: 295–311.
Rabinovitch, M., Manejias, R. E., Russo, M. and Abbey, E. E. 1977. Increased spreading of macrophages from mice treated with interferon inducers. — Cell. Immunol. 29: 86–95.
Reed, L. J. and Muench, H. 1938. A simple method of estimating 50% end points. — Am. J. Hyg. 27: 493–497.
Van der Meer, C., Hofhuis, F. M. A. and Willers, J. M. N. 1977. Killed Listeria monocytogenes becomes protective on addition of polyanions. — Nature (Lond.) 269: 594–595.
Van der Meer, C., Hofhuis, F. M. A. and Willers, J. M. N. 1979. Delayed type hypersensitivity and acquired cellular resistance in mice immunized with killed Listeria monocytogenes and adjuvants. — Immunology 37: 77–82.
Werner, G. H., Maral, R., Floc'h, F. and Jouanne, M. 1977. Toxicological aspects of immunopotentiation by adjuvants and immunostimulating substances. — Bull. Inst. Pasteur 75: 5–84.
Willers, J. M. N., Bloksma, N., Van der Meer, C., Snippe, H., Van Dijk, H., De Reuver, M. J. and Hofhuis, F. M. A. 1979. Regulation of the immune response by macrophages. — Antonie van Leeuwenhoek 45: 41–48.
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Bloksma, N., De Reuver, M.J. & Willers, J.M.N. Impaired macrophage functions as a possible basis of immunomodification by microbial agents, tilorone and dimethyldioctadecylammonium bromide. Antonie van Leeuwenhoek 49, 13–22 (1983). https://doi.org/10.1007/BF00457875
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DOI: https://doi.org/10.1007/BF00457875