Skip to main content
SpringerLink
Log in

Muramyldipeptide and granulocyte-macrophage colony-stimulating factor enhance interferon-γ-induced nitric oxide production by rat alveolar macrophages

  • Molecular Immunopathology
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

Rat alveolar macrophages incubated with recombinant rat interferon-γ producel-arginine-dependent nitric oxide, which is rapidly decomposed into nitrite: this production by interferon-γ was markedly enhanced by granulocyte-macrophage colony-stimulating factor and muramyldipeptide, but not by other cytokines. The enhancement was dependent on the presence ofl-arginine in the incubation medium. It was based on a simple synergism between interferon-γ and muramyldipeptide and a priming effect of granulocyte-macrophage colony-stimulating factor for interferon-γ-induced nitrite production. These data suggest that cytokine networks are important in the induction of nitric oxide in rat alveolar macrophages.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Y. Sibille and H. J. Reynolds,Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am. Rev. Respir. Dis.41, 471–501 (1990).

    Google Scholar 

  2. D. J. Stuehr and M. A. Marletta,Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines, or interferon-γ. J. Immunol.139, 518–525 (1987).

    PubMed  Google Scholar 

  3. J. B. Hibbs, R. R. Taintor and Z. Vavrin,Macrophage cytotoxicity: role for l-arginine deiminase and imino nitrogen oxidation to nitrite, Science235, 473–476 (1987).

    PubMed  Google Scholar 

  4. T. R. Billiar, R. D. Curran, D. J. Stuehr, M. A. West, B. G. Bentz and R. L. Simmons,An l-arginine dependent mechanism mediates Kuppfer cell inhibition of hepatoctye protein synthesis in vitro. J. Exp. Med.169, 1467–1472 (1989).

    PubMed  Google Scholar 

  5. A. H. Ding, C. F. Nathan and D. J. Stuehr,Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages: comparison of activating cytokines and evidence for independent production. J. Immunol.141, 2407–2412 (1988).

    PubMed  Google Scholar 

  6. P. G. Jorens, F. J. Van Overveld, H. Bult, P. A. Vermeire and A. G. Herman,l-arginine-dependent production of nitrogen oxides by rat pulmonary macrophages. Eur. J. Pharmacol.200, 205–209 (1991).

    PubMed  Google Scholar 

  7. T. Schaberg and A. E. Filderman,Colony-stimulating factor induction of protooncogene expression in rat alveolar macrophages. Am. J. Physiol.259, L144-L150 (1990).

    PubMed  Google Scholar 

  8. H. H. H. M. Schmidt, H. Nau, J. Wittfort, J. Gerlach, K. E. Prescher, M. M. Klein, F. Nirooma and E. Böhme,Arginine is a physiological precursor of endothelium-derived nitric oxide. Eur. J. Pharmacol.154, 213–216 (1988).

    PubMed  Google Scholar 

  9. S. S. Gross, D. J. Stuehr, K. Aisaki, E. A. Jaffe, R. Levi and O. W. Griffith,Macrophage and endothelial nitric oxide synthesis: Cell-type selective inhibition by N G-aminoarginine, N G-nitroarginine, and N G-methylarginine. Biochem. Biophys. Res. Commun.170, 96–103 (1990).

    PubMed  Google Scholar 

  10. M. Fridkin and V. A. Najjar,Tuftsin: Its chemistry, biology and clinical potential. Crit. Rev. Biochem. Molec. Biol.24, 1–40 (1989).

    Google Scholar 

  11. J. C. Drapier, J. Wietzerbin and J. B. Hibbs,Interferon-γ and tumor necrosis factor induce the l-arginine-dependent cytotoxic effector mechanism in murine macrophages. Eur. J. Immunol.18, 1587–1591 (1988).

    PubMed  Google Scholar 

  12. G. M. Barratt, K. Raddassi, J. F. Petit and J. P. Tenu,MDP and LPS act synergistically to induce arginine-dependent cytostatic activity in rat alveolar macrophages. Int. J. Immunopharmacol.13, 159–165 (1991).

    PubMed  Google Scholar 

  13. S. J. Green, S. Mellouk, S. L. Hoffman, M. S. Meltzer and C. A. Nacy,Cellular mechanism of nonspecific immunity to intracellular infectious pathogens: Cytokine-induced synthesis of toxic nitrogen oxides from l-arginine by macrophages and hepatocytes. Immunol. Lett.25, 15–22 (1990).

    PubMed  Google Scholar 

  14. S. J. Green, C. A. Nacy and M. S. Meltzer,Cytokine-induced synthesis of nitrogen oxides in macrophages. J. Leukoc. Biol.50, 93–103 (1991).

    PubMed  Google Scholar 

  15. F. Y. Liew, Y. Li, A. Severn, S. Millott, J. Schmidt, M. Salter and S. Moncada,A possible novel pathway of regulation by murine T helper type-2 (T h 2)cells of a T h 1cell activity via the modulation of the induction of nitric oxide synthase on macrophages. Eur. J. Immunol.21, 2489–2494 (1991).

    PubMed  Google Scholar 

  16. T. J. Standiford, R. M. Strieter, S. W. Chensue, J. Westrick, K. Kasahara and S. L. Kunkel,IL-4 inhibits the expression of IL-8 from stimulated human monocytes. J. Immunol.145, 1435–1439 (1990).

    PubMed  Google Scholar 

  17. J. Hasagaria, A. Sato, K. Chida, Y. Nakano, I. Shichi, R. Tamura and T. Suda,The efficacy of synthetic muramyl dipeptide in augmenting the antibacterial activity of the bronchoalveolar cells. Am. Rev. Respir. Dis.145, A335 (1992).

    Google Scholar 

  18. K. B. Glaser, R. Asmis and E. A. Dennis,Bacterial lipopolysaccharide priming of P388D 1 macrophage-like cells for enhanced arachidonic acid metabolism. J. Biol. Chem.265, 8658–8664 (1990).

    PubMed  Google Scholar 

  19. J. M. Cavaillon, C. Fitting and N. Haeffner-Cavaillon,Recombinant C5a enhances interleukin-1 and tumor necrosis factor release by lipopolysaccharide-stimulated monocytes and macrophages. Eur. J. Immunol.20, 253–257 (1990).

    PubMed  Google Scholar 

  20. J. A. Rankin, C. E. Schrader, S. M. Smith and R. A. Lewis,Recombinant interferon-gamma primes alveolar macrophages cultures in vitro for the release of leukotriene B4 in response to IgG stimulation. J. Clin. Invest.83, 1691–1700 (1989).

    PubMed  Google Scholar 

  21. I. J. Amler, J. B. Hibbs Jr, C. J. Parker, B. B. Johnson, R. R. Taintor and Z. Vavrin,Activated macrophage condition medium: Identification of the soluble factors inducing cytotoxicity and the l-arginine dependent effector mechanism. J. Leukoc. Biol.49, 610–620 (1991).

    PubMed  Google Scholar 

  22. G. L. Gustafson and M. J. Rhodes,A rationale for the prophylactic use of monophosphoryl lipid A in sepsis and septic shock. Biochem. Biophys. Res. Commun.182, 269–275 (1992).

    PubMed  Google Scholar 

  23. A. E. Huot and M. D. Hacker,Role of reactive nitrogen intermediate production in alveolar macrophage-mediated cytostatic activity induced by bleomycin lung damage in rats. Cancer Res.50, 7863–7866 (1990).

    PubMed  Google Scholar 

  24. M. Denis,Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent mycobacterium avium and to kill avirulent M. Avium: Killing effector mechanism depends on the generation of reactive nitrogen intermediates. J. Leukoc. Biol.49, 380–387 (1991).

    PubMed  Google Scholar 

  25. R. M. Rose, L. Kobzik, A. E. Filderman, M. W. Vermeulen, K. Dushay and R. E. Donahue,Characterization of colony stimulating factor activity in the human respiratory tract. Am. Rev. Respir. Dis.145, 394–399 (1992).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Respiratory Medicine, University of Antwerp (UIA), Universiteitsplein 1, B-2610, Antwerp (Wilrijk), Belgium

    Philippe G. Jorens, Frans J. van Overveld & Paul A. Vermeire

  2. Department of Pharmacology, University of Antwerp (UIA), Universiteitsplein 1, B-2610, Antwerp (Wilrijk), Belgium

    Hidde Bult & Arnold G. Herman

Authors
  1. Philippe G. Jorens
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frans J. van Overveld
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hidde Bult
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul A. Vermeire
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arnold G. Herman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jorens, P.G., van Overveld, F.J., Bult, H. et al. Muramyldipeptide and granulocyte-macrophage colony-stimulating factor enhance interferon-γ-induced nitric oxide production by rat alveolar macrophages. Agents and Actions 38 (Suppl 1), 100–105 (1993). https://doi.org/10.1007/BF02027220

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02027220

Keywords

Search

Navigation