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Modulation of natural killer cytotoxicity by muramyl dipeptide and trehalose dimycolate incorporated in squalane droplets

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Summary

The effect on natural killer (NK) cytotoxicity of splenic cells from BALB/c mice pretreated i. v. with squalane-in-water preparations of muramyl dipeptide (MDP), trehalose dimycolate (TDM), or the combination of MDP-plus-TDM was investigated. MDP or TDM augmented the NK cytotoxicity which peaked 48 h after the pretreatment whereas the combination of MDP and TDM induced an inhibition of the NK activity. Infection with influenza virus, a potent stimulator of NK cells, after the pretreatment with biological response modifiers resulted in a markedly enhanced NK activity on day 2 in MDP and control groups. Mice pretreated with TDM or the combination of MDP and TDM showed only moderate NK activity which peaked on day 3 after influenza infection. The NK activity was susceptible to asialo GM1 and complement treatment. The cytotoxicity of MDP-plus-TDM cells could be significantly enhanced after treatment with anti-macrophage monoclonal antibody and complement. NK activity induced by MDP or TDM was reduced by mixing MDP-plus-TDM cells. Addition of adherent cell-depleted MDP-plus-TDM suspension to MDP or TDM cells had a NK restorative effect. Splenic cells from mice pretreated 2 days earlier with MDP or TDM, but not MDP-plus-TDM, generated enhanced levels of luminol-dependent chemiluminescence.

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References

  1. 1.

    Bash JA, Vogel D (1984) Cellular immunosencence in F 344 rats: decreased natural killer (NK) cell activity involves changes in regulatory interactions between NK cells, interferon, prostaglandin and macrophages. Mech Ageing Dev 24:49–65

  2. 2.

    Biron CA, Welsh RM (1982) Activation and role of natural killer cells in virus infections. Med Microbiol Immunol 170:155–172

  3. 3.

    Braun DP, Penn RD, Harris JE (1984) Regulation of natural killer cell function by glass-adherent cells in patients with primary intracranial malignancies. Neurosurgery 15:29–33

  4. 4.

    Brunda MJ, Herberman RB, Holden HT (1980) Inhibition of murine natural killer cell activity by prostaglandin. J Immunol 124:2682

  5. 5.

    Carelli C, Audibert F, Chedid L (1981) Persistent enhancement of cell-mediated and antibody immune responses after administration of muramyl dipeptide derivatives with antigen in metabolizable oil. Infect Immun 33:312–314

  6. 6.

    Combe B, Pope, Darnell B, Kincaid W, Tatal N (1984) Regulation of natural killer cell activity by macrophages in the rheumatoid joint and peripheral blood. J Immunol 133:709–713

  7. 7.

    Djeu JY, Heinbaugh JA, Holden HT, Herberman RB (1979) Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol 122:175–181

  8. 8.

    Fidler IJ (1986) Optimization and limitations of systemic treatment of murine melanoma metastases with liposomes containing muramyl tripeptide phosphatidylethanolamine. Cancer Immunol Immunother 21:169–173

  9. 9.

    Gorelik E, Wiltrout RH, Brunda MJ, Bere WE, Herberman RB (1985) Influence of adoptively transferred thioglycollate-elicited peritoneal macrophages on metastasis formation in mice with depressed or stimulated NK activity. Clin Exp Metastasis 3:111–123

  10. 10.

    Granger DL, Yamamoto K, Ribi E (1976) Delayed hypersensitivity and granulomatous response after immunization with protein antigens associated with a mycobacterial glycolipid and oil droplets. J Immunol 116:482–488

  11. 11.

    Herberman RB (ed) (1982) NK cells and other natural effector cells. Academic Press, New York

  12. 12.

    Herberman RB, Ortaldo JR (1981) Natural killer cells: their role in defence against disease. Science 214:24–30

  13. 13.

    Ito M, Ralph P, Moore MAS (1980) Suppression of spleen natural killing activity induced by BCG. Clin Immunol Immunopathol 16:30–38

  14. 14.

    Lederer E, Chedid L (1982) Immunomodulation by synthetic muramyl dipeptides and trehalose diesters: In: Immunological approaches to cancer therapeutics. John Wiley & Sons Inc, New York, p 107–135

  15. 15.

    Leung KN, Ada GL (1981) Induction of natural killer cells during murine influenza virus infection. Immunobiology 160:352–366

  16. 16.

    Masihi KN, Brehmer W, Lange W, Ribi E (1983) Effects of mycobacterial fractions and muramyl dipeptide on the resistance of mice to aerogenic influenza virus infection. Int J Immunopharmacol 5:403–410

  17. 17.

    Masihi KN, Brehmer W, Azuma I, Lange W, Müller S (1984) Stimulation of chemiluminescence and resistance against aerogenic influenza virus infection by synthetic muramyl dipeptide combined with trehalose dimycolate. Infect Immun 43:233–237

  18. 18.

    Masihi KN, Brehmer W, Lange W, Ribi E, Schwartzman S (1984) Protective effect of muramyl dipeptide analogs in combination with trehalose dimycolate against aerogenic influenza virus and Mycobacterium tuberculosis infections in mice. J Biol Response Mod 3:663–671

  19. 19.

    Masihi KN, Bhaduri CR, Werner H, Janitschke K, Lange W (1986) Effects of muramyl dipeptide and trehalose dimycolate on resistance of mice to Toxoplasma gondii and Acanthamoeba culbertsoni infections. Int Arch Allergy Appl Immunol 81:112–117

  20. 20.

    McLaughlin CA, Schwartzman SM, Horner BL, Jones GH, Moffatt JG, Nestor JJ, Tegg D (1980) Regression of tumors in guinea pigs after treatment with synthetic muramyl dipeptides and trehalose dimycolate. Science 208:415–416

  21. 21.

    Milisauskas VK, Cudkowicz G, Nakamura I (1983) Cellular suppression of murine ADCC and NK activities induced by Corynebacterium parvum. Cancer Immunol Immunother 15:149–154

  22. 22.

    Nasralla AG, Gallagher MT, Priest EL, Trentin JJ (1980) Comparative effects of different strains of Coryebacterium parvum on natural cell-mediated cytotoxicity. Cancer Res 40:4159–4164

  23. 23.

    Ortaldo JR, Mason AT, Gerard JP, Hernderson LE, Farrar W, Hopkins RF, Herberman RB, Rabin H (1984) Effects of natural and recombinant IL 2 on regulation of IFNγ production and natural killer activity: lack of involvement of the TAC antigen for these immunoregulatory effects. J Immunol 133:779–783

  24. 24.

    Savary CA, Lotzova E (1978) Suppression of natural killer cell cytotoxicity by splenocytes from Corynebacterium parvum-injected, bone marrow-tolerant, and infant mice. J Immunol 120:239–243

  25. 25.

    Sharma SD, Tsai V, Krahenbuhl SL, Remington JS (1981) Augmentation of mouse natural killer activity by muramyl dipeptide and its analogs. Cell Immunol 62:101–109

  26. 26.

    Talmadge JE, Schneider M, Collins M, Phillips H, Herberman RB, Wiltrout RH (1985) Augmentation of NK cell activity to tissue specific sites by liposomes incorporating MTP-PE. J Immunol 135:1477–1483

  27. 27.

    Wolfe SA, Tracey DE, Henney CS (1976) Induction of „natural killer“ cells by BCG. Nature 262:584–586

  28. 28.

    Yamamoto H, Fuyama S, Arai S, Sendo F (1985) Inhibition of mouse natural killer cytotoxicity by heparin. Cell Immunol 96:409–417

  29. 29.

    Yanagihara RH, Adler WH (1982) Inhibition of mouse natural killer activity by cyclosporin A. Immunology 45:325–332

  30. 30.

    Yang J, Zucker-Franklin D (1984) Modulation of natural killer (NK) cells by autologous neutrophils and monocytes. Cell Immunol 86:171

  31. 31.

    Yarkoni E, Lederer E, Rapp HJ (1981) Immunotherapy of experimental cancer with a mixture of synthetic muramyl dipeptide and trehalose dimycolate. Infect Immun 32:273–276

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Correspondence to K. Noel Masihi.

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Masihi, K.N., Lange, W. & Rohde-Schulz, B. Modulation of natural killer cytotoxicity by muramyl dipeptide and trehalose dimycolate incorporated in squalane droplets. Cancer Immunol Immunother 24, 19–24 (1987). https://doi.org/10.1007/BF00199828

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Keywords

  • Influenza
  • Natural Killer
  • Natural Killer Cell
  • Influenza Virus
  • Trehalose