Lymphocyte Activation, Iron Uptake and Release by Human Mononuclear Leukocytes in Tiie Presence of Desferrioxamine

Abstract

Desferrioxamine (DFO), an iron chelating drug, has been shown to inhibit the proliferative response of leukocytes to mitogen. In the present study we investigated the effect of DFO on different aspects of human mononuclear leukocyte (MNL) function in vitro. DFO, added at the beginning of the culture period, inhibited both tritiated thymidine and radioiron uptake by phytohemagglu tinin-stimulated MNL and the degree of inhibition correlated with the degree of cellular activation, to the extent that in the absence of mitogen a significant stimulatory effect of DFO was observed, especially when iron supplement was present in the culture medium. However DFO was not found to inhibit iron uptake directly, and relatively low concentrations of iron as iron-transferrin totally reversed the inhibitory action of DFO on thymidine uptake. Although the release of iron from preloaded MNL in the presence of DFO was only 15% greater than the spontaneous release of control cultures, we conclude that the site of action of DFO is an intracellular iron pool, that increases in importance when the supply of iron to the cellular iron metabolism become limiting as in optimally activated MNL.