Selective induction of mononuclear phagocytes to produce neopterin by interferons

Gabriele Bitterlich, Gyängyi Szabó, Ernst R. Werner, Clara Larcher, Dietmar Fuchs, Arno Hausen, Gilbert Reibnegger, Thomas F. Schulz, Jakob Troppmair, Helmut Wachter, Manfred P. Dierich

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46 Citations (Scopus)

Abstract

Interferon-gamma (IFN-γ) has been shown to be a potent inducer of neopterin secretion by human peripheral blood monocytes/macrophages (1). In this paper, it is shown that other known stimuli of monocytes (e.g., to secrete proteases or to migrate) such as zymosanactivated human serum, lipopolysaccharide, human C3/iC3 and zymosan coated with complement were unable to trigger monocytes/macrophages to release neopterin. Monocytes/ macrophages could be stimulated solely by IFN-γ (25 U/ml) and IFN-α at very high concentrations (10,000 U/ml). In the case of human peripheral blood mononuclear cells (PBMNC), basically the same pattern was observed. If however, in the buffer controls PBMNC showed some neopterin release, all stimuli triggered an increase of neopterin secretion: 10,000 U/ml IFN-α induced the same amount of secreted neopterin as did 25 U/ml of IFN-γ. Both caused higher levels of neopterin secretion than ZAS, LPS and C3/iC3. Amongst the supernatants from PBMNC, only those which were obtained from cells activated with IFN-γ or -a stimulated monocytes/macrophages to produce neopterin. Supernatants from lymphocytes activated with zymosan, lipopolysaccharide and interferon did not contain neopterin, nor did the latter induce monocytes/macrophages to generate and secrete neopterin. Antibodies against IFN-γ inhibited the triggering effect of the supernatants except when generated by IFN-α at 10,000 U/ml. These results demonstrate that both interferons, IFN-γ and IFN-α, the latter only at a 400fold higher concentration, can trigger monocytes/macrophages directly to secrete neopterin. ZAS, LPS and C3/iC3 are weakly effective only on a mixture of lymphocytes and monocytes/ macrophages, provided this cell mixture shows already a basic spontaneous neopterin release. Probably they exert their effect by directly or indirectly liberating interferons.

Original languageEnglish
Pages (from-to)228-235
Number of pages8
JournalImmunobiology
Volume176
Issue number3
DOIs
Publication statusPublished - 1988

Keywords

  • C3
  • IFN-α
  • IFN-γ
  • IL 1
  • IL 2
  • LPS
  • PBMNC
  • TPA
  • ZAS
  • ZX
  • human peripheral blood mononuclear cells
  • interferon-alpha 2C
  • interferon-gamma
  • interleukin 1
  • interleukin 2
  • lipopolysaccharide
  • tetradecanoylphorbolacetate
  • third component of human complement
  • zymosan coated with complement
  • zymosan-activated serum

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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  • Cite this

    Bitterlich, G., Szabó, G., Werner, E. R., Larcher, C., Fuchs, D., Hausen, A., Reibnegger, G., Schulz, T. F., Troppmair, J., Wachter, H., & Dierich, M. P. (1988). Selective induction of mononuclear phagocytes to produce neopterin by interferons. Immunobiology, 176(3), 228-235. https://doi.org/10.1016/S0171-2985(88)80055-X