Activation of human monocyte-derived macrophages by interferon gamma is accompanied by increase of poly(ADP-ribose) polymerase activity

Biochim Biophys Acta. 1991 Jan 10;1091(1):101-9. doi: 10.1016/0167-4889(91)90228-p.

Abstract

We have investigated poly(ADP-ribosyl)ation processes in human monocyte-derived macrophages and the effect of the activating cytokine, interferon gamma (IFN-gamma) on these processes. IFN-gamma was shown to increase the activity of poly(ADP-ribose) polymerase in human macrophages. A 2-3-fold enhancement of poly(ADP-ribose) polymerase activity was observed after 3-4 h of incubation with IFN-gamma, whose effects were dose-dependent and maximal at 20-50 U/ml. Staining with anti-poly(ADP-ribose) antibodies and purification of ADP-ribosylated nuclear proteins by affinity chromatography over boronate agarose showed that enhancement of poly(ADP-ribose) polymerase activity by IFN-gamma was accompanied by accumulation of poly(ADP-ribose) polymers in nuclear proteins. The effects of IFN-gamma on poly(ADP-ribose) polymerase activity were not due to an enhanced accumulation of the message for the enzyme, indicating that the activation of the enzyme activity was due to post-transcriptional modifications. IFN-gamma was shown to induce DNA strand breaks in human macrophages. This phenomenon followed the same time-course and was evident with the same doses of IFN-gamma that increased poly(ADP-ribose) polymerase activity. Since poly(ADP-ribose) polymerase is known to require DNA nicks for its activity, the capability of IFN-gamma to induce DNA strand breaks can explain its effects on poly(ADP-ribosyl)ation processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Damage
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / physiology*
  • Macrophage Activation / drug effects
  • Macrophage Activation / physiology*
  • Macrophages / enzymology*
  • Monocytes / enzymology*
  • Nuclear Proteins / metabolism
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism*

Substances

  • Nuclear Proteins
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly Adenosine Diphosphate Ribose
  • Interferon-gamma
  • Poly(ADP-ribose) Polymerases