EFFECTS OF ANTIOXIDANTS ON ORNITHINE DECARBOXYLASE IN MITOGENICALLY-ACTIVATED LYMPHOCYTES-T

Reactive oxygen species formation is an early event following lymphocyte activation and may trigger other biochemical processes. Anti-oxidants (desferrioxamine (DES), nordihydroguaiaretic acid (NDGA) and potassium ferricyanide) inhibit human and murine T cell proliferation in vitro. Since an increase in ornithine decarboxylase (ODC) activity is an essential concomitant of T lymphocyte proliferation, we have examined in vitro the effects of anti-oxidants on this activity increase. ODC activity in mouse lymph node T cells increased steadily from 6-24 h after addition of concanavalin A. The combination of phorbol myristate acetate (PMA) and ionomycin also stimulated ODC activity in these cells. The anti-oxidants DES, NDGA and ferricyanide strongly inhibited the increase in ODC activity seen in response to either concanavalin A or PMA/ionomycin. Dose-response curves for the inhibitory effects of the anti-oxidants on DNA synthesis and ODC activity at 48 h after mitogen addition were very similar. Addition of putrescine or spermidine (10-1000-mu-M) could not overcome the block in DNA synthesis induced by DES. Although the anti-oxidants inhibited the ODC activity increase in mitogen-stimulated T cells, they did not decrease mRNA levels for the enzyme. These results suggest that intracellular formation of reactive oxygen species is involved in the induction of ODC activity by a mechanism exerted at a posttranscriptional stage. The anti-oxidants can be employed as tools to elucidate contingent relationships between some intracellular events that follow T cell activation.