concanavalin-a and acridone

6(5H)-phenanthridinone, a recently identified poly(ADP-ribose)polymerase (PARP) inhibitor, is able, at micromolar concentrations, to inhibit concanavalin A-induced lymphocyte proliferation and to potentiate the effect of gamma radiation upon murine spleen cells. When added at the onset of a mixed lymphocyte culture, this compound strongly depresses the induction of primary allogeneic (anti-H2k) cytotoxic T-lymphocytes (CTLs). Lymphokine-activated killer (LAK) induction was also found to be impaired by the PARP inhibitor. Taken together, these results clearly indicate that PARP plays a key-role in immune reactions involving cytotoxicity and that 6(5H)-phenanthridinone could be considered as a potent immunomodulator.

Topics: Acridines; Acridones; Animals; Benzamides; Cells, Cultured; Concanavalin A; Female; Gamma Rays; Immunosuppressive Agents; Interleukin-2; Isoquinolines; Killer Cells, Lymphokine-Activated; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Mice; Mice, Inbred C3H; Mice, Inbred DBA; Phenanthrenes; Poly(ADP-ribose) Polymerase Inhibitors; Recombinant Proteins; Spleen; T-Lymphocytes, Cytotoxic