Horse spleen ferritin inhibits superoxide production by equine blood monocytes in vitro

The effect of horse spleen ferritin (HFR) on the production of superoxide anion (O2) by equine blood monocytes was investigated. Preincubation of monocytes with HFR resulted in pronounced inhibition of O2- production in response to phorbol 12-myristate 13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP), and opsonized zymosan (OZ). The inhibitory effect of HFR upon stimulation of monocytes with PMA was both dose and time dependent. Maximum inhibition (90%) was observed after preincubation of monocytes with HFR (2 mg/ml) for 18 h before stimulation with PMA. ApoHFR at the same concentration showed only about one-third of the inhibitory effect of iron-saturated HFR. Various iron complexes, such as iron dextran, hemin, or ferric ammonium sulfate, had no significant effect on O2- production by monocytes. Neither catalase (Cat) nor desferrioxamine (DFO) changed the inhibitory effect of HFR. These findings suggest that HFR may play an important role in inhibition of superoxide generation by equine monocytes. Although the mechanism of this inhibition remains unknown, the results obtained suggest that it is not due to ferritin-dependent oxidative inactivation of the NADPH-oxidase system in stimulated monocytes.