Activation of human monocyte-derived macrophages by interferon gamma is accompanied by increase of poly(ADP-ribose) polymerase activity.
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.
Berton
G
G
Institute of General Pathology, University of Verona, Italy.
Sorio
C
C
Laudanna
C
C
Menegazzi
M
M
Carcereri De Prati
A
A
Suzuki
H
H
D004249:DNA Damage; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology*; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000201:enzymology*; D009000:Monocytes / Q000201:enzymology*; D009687:Nuclear Proteins / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D009687:Nuclear Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011064:Poly Adenosine Diphosphate Ribose; D007371:Interferon-gamma; D011065:Poly(ADP-ribose) Polymerases