Skip to main content

In vivo and in vitro modulation of NK and ADCC activities of mouse spleen cells by peptidoglycan monomer (PGM)


The ability of peptidoglycan monomer (PGM), an immunomodulator obtained fromBrevibacterium divaricatum, to modulate NK and ADCC activities of spleen cells was tested in mice with constitutively weak (C57B1) or strong NK activity (CBA, C3H). In weak reactors, i.v. injection of PGM enhanced the NK and ADCC activity as effectively as a known stimulator, poly I.C, and the dynamics of the response was comparable. In strong reactors, PGM caused two peaks of the ADCC response, and one peak of NK stimulation (after an initial decline), whereas poly I.C caused more or less persistent stimulation of both activities. Incubation of spleen cells with PGM was generally less effective than the treatment in vivo. No alteration of NK activity was recorded at high effector-to-target ratio (E:T), and at low ones, PGM caused suppression. This was true both for weakly and strongly reactive cells. ADCC was either unchanged (CBA spleen cells), stimulated (C3H), or suppressed at high E:T and enhanced at low E:T (C57B1). PGM apparently activates an interlocked regulatory mechanism, and the final outcome probably depends on relative concentrations of regulatory and effector cells and on their per cell activities. Hence the effect varied with the time interval between treatment and assay, with strain-related constitutive reactivity, and with the E:T ratio.

This is a preview of subscription content, access via your institution.



antibody-dependent cellular cytotoxicity




Interleukin 1


interleukin 2


muramyl dipeptide


natural killer


plaque-forming cell


peptidoglycan monomer

poly I.C:

polyinosinic-polycytidylic acid


  1. 1.

    Adam A, Petit J-F, Lefrancier P, Lederer E (1981) Muramyl peptides. Chemical structure, biological activity and mechanism of action. Molec Cell Biochem 41:27–47

    PubMed  Google Scholar 

  2. 2.

    Chedid L (1986) Neuroimmunopharmacological activities of muramyl peptides. In: Cinader B, Miller RG (eds) Progress in immunology, vol 6. Academic Press, Orlando, p915

    Google Scholar 

  3. 3.

    Goguel A-F, Payelle B, Lespinats G, Nauciel C (1983) Cytotoxic responses induced by peptidoglycans with or without in vivo antitumor activity. JNCI 71:325–330

    PubMed  Google Scholar 

  4. 4.

    Goguel A-F, Lespinats G, Nauciel C (1982) Peptidoglycan extracted from gram-positive bacteria: Expression of antitumor activity according to peptide structure and route of injection. JNCI 68:657–663

    PubMed  Google Scholar 

  5. 5.

    Hanna N, Fidler IJ (1980) Role of natural killer cells in the destruction of circulating tumor emboli. JNCI 65:801–809

    PubMed  Google Scholar 

  6. 6.

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

    PubMed  Google Scholar 

  7. 7.

    Hršak I, Tomašić J, Pavelić K, Benković B (1979) On the mechanism of immunostimulatory activity of monomeric peptidoglycans. Period Biol 81:155–157

    Google Scholar 

  8. 8.

    Hršak I, Tomašić J, Pavelić K, Valinger Z (1979) Stimulation of humoral immunity by peptidoglycan monomer fromBrevibacterium divaricatum. Z Immun Forsch 155:312–318

    Google Scholar 

  9. 9.

    Hršak I, Novak Đ, Tomašić J (1980) Immunostimulating activity of peptidoglycan monomer (PGM) on in vivo primary response to sheep erythrocytes,Salmonella typhimurium and Newcastle disease virus. Period Biol 82:147–151

    Google Scholar 

  10. 10.

    Hršak I, Tomašić J, Osmak M (1983) Immunotherapy of B-16 melanoma with peptidoglycan monomer. Eur J Cancer Clin Oncol 19:681–686

    PubMed  Google Scholar 

  11. 11.

    Keglević D, Ladešić B, Tomašić J, Valinger Z, Naumski R (1979) Isolation procedure and properties of monomer unit from lysozyme digest of peptidoglycan complex exerted into the medium of penicillin-treatedBrevibacterium divaricatum mutant. Biochim Biophys Acta 585:273–281

    PubMed  Google Scholar 

  12. 12.

    Leclerc C, Juy D, Chedid L (1979) Inhibitory and stimulatory effects of synthetic glycopeptide (MDP) on the in vitro PFC response: factors affecting the response. Cell Immunol 42:336–343

    PubMed  Google Scholar 

  13. 13.

    Le Garrec Y, Morin A (1987) Modulation of natural killer activity by muramyl peptides: relationship with adjuvant anti-infectious properties. Natl Immunol Cell Growth Regul 6:65–76

    Google Scholar 

  14. 14.

    Masihi KN, Lange W, Rohde-Schulz B (1987) Modulation of natural killer cytotoxicity by muramyl dipeptide and trehalose dimycolate incorporated in squalene droplets. Cancer Immunol Immunother 24:19–24

    PubMed  Google Scholar 

  15. 15.

    Merrill JE (1983) Natural Killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities can be differentiated by their different sensitivities to interferon and prostaglandin E1. J Clin Immunol 3:42–50

    PubMed  Google Scholar 

  16. 16.

    Pavelić K, Bernacki RJ, Vuk-Pavlović S (1987) Insulin-modulated interleukin-2 production by murine splenocytes and T-cell hybridoma. J Endocrinol 114:89–94

    PubMed  Google Scholar 

  17. 17.

    Rakočević S (1986) Nonspecific active immunotherapy of a fibrosarcoma based on monitoring specific immune reaction and phagocytosis in tumor-bearing mice. Thesis, University of Zagreb, Faculty of Veterinary Medicine

  18. 18.

    Räsänen L, Arvilommi H (1982) Cell walls, peptidoglycans, and teichoic acid of grammpositive bacteria as polyclonal inducers and immunomodulators of proliferative and lymphokine responses of human B- and T-lymphocytes. Infect Immun 35:523–527

    PubMed  Google Scholar 

  19. 19.

    Sava G, Giraldi T, Tomašić J, Hršak I (1983) Immunotherapy of Lewis lung carcinoma with hydrosoluble peptidoglycan monomer (PGM). Cancer Immunol Immunother 15:84–86

    PubMed  Google Scholar 

  20. 20.

    Sava G, Tomašić J, Hršak I (1984) Antitumor and antimetastatic activity of the immunoadjuvant peptidoglycan monomer PGM in mice bearing MCa mammary carcinoma. Cancer Immunol Immunother 18:49–53

    PubMed  Google Scholar 

  21. 21.

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

    PubMed  Google Scholar 

  22. 22.

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

    PubMed  Google Scholar 

  23. 23.

    Taniyama T, Holden HT (1979) Direct augmentation of cytolitic activity of tumor-derived macrophages and macrophage cell lines by muramyl dipeptide. Cell Immunol 48:369–374

    PubMed  Google Scholar 

  24. 24.

    Vermeulen MW, David JR, Remold HG (1987) Differential mRNA responses in human macrophages activated by interferon-γ and muramyl dipeptide. J Immunol 139:7–9

    PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to J. Gabrilovac.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Gabrilovac, J., Tomašić, J., Boranić, M. et al. In vivo and in vitro modulation of NK and ADCC activities of mouse spleen cells by peptidoglycan monomer (PGM). Res. Exp. Med. 189, 265–273 (1989).

Download citation

Key words

  • Peptidoglycan monomer (PGM)
  • NK and ADCC activity
  • Immunomodulation