European Journal of Clinical Pharmacology

, Volume 30, Issue 1, pp 99–104 | Cite as

Augmentation of human blood monocyte microbicidal activity by RU 41740, a glycoprotein extract fromKlebsiella pneumoniae

  • H. Nielsen
Originals

Summary

Non-specific activation of host defences may have a significant impact on the outcome of infections in the immunocompromized patient. RU 41740, a glycoprotein extract fromKlebsiella pneumoniae, effective in increasing resistance to experimental infections in animals, has been examined in vitro for its effect on human blood monocyte locomotion, phagocytosis, killing ofCandida albicans, and release of superoxide anion.

RU 41740 had no chemo-attractant activity nor any effect on monocyte chemotactic and phagocytic function.

Candidacidal capacity and superoxide anion production by monocytes were significantly enhanced after preincubation with RU 41740 >1.0 µg/ml.

The effect was dose- and time-dependent and was not influenced by the presence of lymphocytes or their culture supernatants.

This suggests a direct interaction with monocytes as the mechanism of action of the extract.

Key words

RU 41740 Candida albicans chemotaxis monocyte locomotion superoxide production candidacidal activity 

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References

  1. 1.
    Boutin C, Viallat JR, Costantini D, Farisse P, Edelstein R (1983) Effect of RU 41740, a purified immune modulating compound extract fromKlebsiella pneumoniae, on the frequency and severity of acute infectious exacerbations in patients with chronic bronchitis. Proceedings of 13th International Congress of Chemotherapy, ViennaGoogle Scholar
  2. 2.
    Brossard C, Smets P, Zalisz R, Edelstein R (1983) Synergism between the immunopotentiator RU 41740 and ampicillin in lethalListeria monocytogenes andStaphylococcus aureus infections in mice. Proceedings of 13th International Congress of Chemotherapy, ViennaGoogle Scholar
  3. 3.
    Bruvier C, Zalisz R, Smets P, Guenounou M, Montreuil J, Fournet B (1985) Biochemical analysis of RU 41740, a glycoproteic immunomodulating agent fromKlebsiella pneumoniae. FEBS LettGoogle Scholar
  4. 4.
    Cummings NP, Pabst MJ, Johnston RB (1980) Activation of macrophages for enhanced release of superoxide anion and greater killing ofCandida albicans by injection of muramyl dipeptide. J Exp Med 152: 1659–1669Google Scholar
  5. 5.
    Dickneite G, Kaspereit F, Sedlacek HH (1984) Stimulation of cell-mediated immunity by bestatin correlates with reduction of bacterial persistence in experimental chronicSalmonella typhimurium infection. Infect. Immunology 44: 168–174Google Scholar
  6. 6.
    Griscelli C, Grospierre B, Montrevil J, Fournet B, Bruvier G, Lang JM, Marchiani C, Zalisz R, Edelstein R (1982) Immunomodulation by glycoprotein fractions isolated fromKlebsiella pneumoniae, 261–265. In: Yamamura Y, Kotani S (eds) Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, AmsterdamGoogle Scholar
  7. 7.
    Hashimoto S, Nomoto K, Matsuzaki T, Yokokura T, Mutai M (1984) Oxygen radical production by peritoneal macrophages and kupffer cells elicited withBactobacillus casei, Infect Immun 44: 61–67Google Scholar
  8. 8.
    Hedegaard HB, Pabst MJ (1982) Preservation of superoxide anion-generating capacity in cultured human monocytes treatment with muramyl dipeptide or lipopolysaccharide, 205–208. In: Yamamura Y, Kotani S (eds) Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, AmsterdamGoogle Scholar
  9. 9.
    Imai K, Tanaka A (1981) Effect of muramyl dipeptide, a synthetic bacterial adjuvant, on enzyme release from cultured mouse macrophages. Microbiol Immonol 25: 51–62Google Scholar
  10. 10.
    Iribe H, Koga T, Onove K, Kotani S, Kusomoto S, Shiba T (1984) Macrophage-stimulating effect of a synthetic muramyl dipeptide and its adjuvant-active and in-active analogs for the production of T-cell activating monokines. Cell Immonol 64: 73–83Google Scholar
  11. 11.
    Nathan CF (1982) Secretion of oxygen intermediators: Role in effector functions of activated macrophages. Fed Proc 41: 2206–2211Google Scholar
  12. 12.
    Nielsen H, Olesen Larsen S (1983) Human monocyte chemotaxis in vitro. Influence of in vitro variables in the filter assay. Acta Pathol Microbiol Immunol Scand [C] 91: 109–115Google Scholar
  13. 13.
    Ogawa T, Kotani S, Fukuda K, Tsukamoto Y, Mori M, Kusumoto S, Shiba T (1982) Stimulation of migration of human monocytes by bacterial cell walls and muramyl peptides. Infect Immun 38: 817–824Google Scholar
  14. 14.
    Pabst MJ, Johnston RB (1980) Increased production of superoxide anion by macrophages exposed in vitro to muramyl dipeptide or lipopolysaccharide J Exp Med 151: 101–114Google Scholar
  15. 15.
    Paurant M, Parant F, Chedid L (1978) Enhancement of the neonate's nonspecific immunity toKlebsiella infection by muramyl dipeptide, a synthetic immunoadjuvant. Proc Natl Acad Sci USA 75: 3395–3399Google Scholar
  16. 16.
    Saito H, Tomioko H (1979) Enhanced hydrogen peroxide release from macrophages stimulated with streptococcal preparation OK-432 Infect. Immunology 26: 779–782Google Scholar
  17. 17.
    Salles MF, Zalisz R, Smets P, Edelstein R (1983) Immunoprophylactic treatment with RU 41740 increases survival of mice lethally infected withCanadida albicans. Proceedings of 13th International Congress of Chemotherapy, ViennaGoogle Scholar
  18. 18.
    Scheinberg MA, Masuda A, Maluf JA, Mendes NF (1978) Monocyte function in patients with solid neoplasms during immunotherapy withCorynebacterium parvum. Cancer 41: 1761–1764Google Scholar
  19. 19.
    Scharlemmer HU, Bosslet K, Sedlacek HH (1983) Ability of the immunomodulating dipeptide bestatin to activate cytotoxic mononuclear phagocytes. Cancer Res 43: 4148–4153Google Scholar
  20. 20.
    Serrou B, Cupissol D, Flad H, Goutner A, Lang JM, Spirzglas H, Plange R, Beltzer M, Challet P, Mathe E (1980) Evaluation of the immunorestorative properties of bestatin in patients with advanced solid tumour. Scand J Immunol 12: 541Google Scholar
  21. 21.
    Sher NA, Poplack DG, Blaese RM, Brown TM, Chaparus SD (1977) Effect ofCorynebacterium parvum, methanol-extraction residue of BCG, and levamisole on macrophage random migration, chemotaxis, and pinocytosis. J Natl Cancer Inst 58: 1753–1757Google Scholar
  22. 22.
    Smialowicz RJ, Schwab JH (1977) Cytotoxicity of rat macrophages activated by persistent or biodegradable bacterial cell walls. Infect Immun 17: 599–606Google Scholar
  23. 23.
    Sone S, Fidler IJ (1980) Synergistic activation by lymphokines and muramyl dipeptide of tumoricidal properties in rat alveolar macrophages. J Immunol 125: 2454–2460Google Scholar
  24. 24.
    Takada H, Tsujimoto M, Ogawa T, Ishihara Y, Kawasaki A, Kotani S, Tanaka A, Nagao S, Kushima K, Fugiki T, Kato A (1982) Immunomodulating activities of biostim, 266–269. In: Yamamura Y, Kotani S (eds) Immunomodulation by microbial products and related synthetic compounds. Excerpta Medica, AmsterdamGoogle Scholar
  25. 25.
    Takada H, Tsujimoto M, Kato K et al. (1979) Macrophage activation by bacterial cell walls and related synthetic compounds. Infect. Immunology 25: 48–53Google Scholar
  26. 26.
    Taniyama T, Holden HT (1979) Direct augmentation of cytolytic activity of tumor-derived macrophages and macrophage cell-lines by muramyl dipeptide. Cell Immunol 48: 369–374Google Scholar
  27. 27.
    Territo MC, Cline MJ (1977) Monocyte function in man. J Immunol 118: 187–192Google Scholar
  28. 28.
    Yam LT, Li CY, Crosby WH (1971) Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol 55: 283–290Google Scholar
  29. 29.
    Zalisz R, Salles MF, Smets P, Brossard C, Rudent A, Edelstein R (1983) Immunoprophylaxis with RU 41740 increases resistance of mice to experimental bacterial, viral and fungal infection. Proceedings of 13th International Congress of Chemotherapy, ViennaGoogle Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • H. Nielsen
    • 1
  1. 1.Department of Clinical Microbiology, State Serum InstituteRigshospitaletCopenhagenDenmark

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