Role of ADP-Ribosylation in Activated Monocytes/Macrophages

  • Sunna Hauschildt
  • Peter Scheipers
  • Wolfgang Bessler
  • Klaus Schwarz
  • Artur Ullmer
  • Hans-Dieter Flad
  • Holger Heine
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 419)

Abstract

Stimulating monocytes/macrophages with bacterial lipopolysaccharide (LPS) results in TNF-α, IL-1, IL-6 and nitrite (NO2 -) formation. Inhibitors of poly(ADP-ribose)polymerase inhibit release of these mediators by preventing mRNA expression indicating that ADP-ribosylation plays a crucial role in the synthesis of these mediators. Furthermore we present evidence that ADP-ribosylation is involved in modifying cellular proteins. In murine macrophages a 33 kDa cytosolic protein could be identified that in response to LPS changed its state of ADP-ribosylation, and in human monocytes we showed that the inhibitor nicotinamide prevents LPS induced phosphorylation of two cytosolic proteins of 36 kDa and 38 kDa (p36/38) LPS. Taken together these data indicate that protein modification by ADP-ribosylation may control cellular processes involved in distinct steps of monocyte/macrophage activation.

Keywords

Nitrite Adenine Dinucleotide Phospho Nicotinamide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hayaishi, O. & K. Ueda eds. 1982. ADP-Ribosylation Reactions: Biology and Medicine. Academic Press, New York.Google Scholar
  2. 2.
    Tanuma, S., K. Kawashima & H. Endo. 1988. Eukaryotic mono(ADP-ribosyl)transferase that ribosylates GTP-binding regulatory Gi protein. J. Biol. Chem. 263: 5485–5489.PubMedGoogle Scholar
  3. 3.
    Molina Y Vedia, L.B. McDonald, B. Reep, B. Brüne, M. Di Silvio, T.R. Billiar & E.G. Lapetina. 1992. Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehy-drogenase inhibits enzymatic activity and increases endogeneous ADP-ribosylation. J. Biol. Chem. 267: 24929–24932.Google Scholar
  4. 4.
    Wang, J., E. Nemoto, A.Y. Kots, H. Kaslow & G. Dennert. 1994. Regulation of cytotoxic T cells by ectonicotinamide adenine dinucleotide (NAD) correlates with cell surface GPI anchored/arginine ADP-ribosyltransferase. J. Immunol., 153: 4048–4058.PubMedGoogle Scholar
  5. 5.
    Hauschildt, S., P. Scheipers & W.G. Bessler. 1991. Inhibitors of poly(ADP-ribose)poly-merase suppress lipopolysaccharide-induced nitrite formation in macrophages. Biochem. Biophys. Res. Commun. 179: 865–871.PubMedCrossRefGoogle Scholar
  6. 6.
    Hauschildt, S., P. Scheipers & W.G. Bessler. 1994. Lipopolysaccharide-induced change of ADP-ribosylation of cytosolic protein in bone marrow derived macrophages. Biochem. J.297: 17–20.PubMedGoogle Scholar
  7. 7.
    Heine, H., A.J. Ulmer, H.D. Flad & S. Hauschildt. 1995. Lipopolysaccharide-induced change of phosphorylation of two cytosolic proteins in human monocytes is prevented by inhibitors of ADP-ribosylation. J. Immunol. 155: 4899–4908.PubMedGoogle Scholar
  8. 8.
    Pellat-Deceunynek, C, J. Wietzerbin & J.C. Drapier. 1994. Nicotinamide inhibits nitric oxide synthase mRNA induction in activated macrophages. Biochem. J. 297: 53–58.Google Scholar
  9. 9.
    Agarwal, S., B.E. Drysdale & H.S. Shin. 1988. Tumor necrosis factor-mediated cytotoxicity involves ADP-ribosylation. J. Immunol. 140: 4187–4192.PubMedGoogle Scholar
  10. 10.
    Schraufstatter, I.U., PA. Hyslop, D.B. Hinshaw, R.G. Spragg, L.A. Sklar & C.G. Cochrane. 1986. Hydrogen peroxid-induced injury of cells and its prevention by inhibitors of poly(ADP-ribose)polymerase. Proc. Natl. Acad. Sci. 83: 4908–4912.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Sunna Hauschildt
    • 1
  • Peter Scheipers
    • 2
  • Wolfgang Bessler
    • 2
  • Klaus Schwarz
    • 1
  • Artur Ullmer
    • 3
  • Hans-Dieter Flad
    • 3
  • Holger Heine
    • 3
  1. 1.Universität Leipzig Institut für Zoologie ImmunbiologieLeipzigGermany
  2. 2.Universität Freiburg Institut für ImmunbiologieFreiburgGermany
  3. 3.Forschungszentrum BorstelBorstelGermany

Personalised recommendations