HORSE SPLEEN FERRITIN INHIBITS SUPEROXIDE PRODUCTION BY EQUINE BLOOD MONOCYTES IN-VITRO

The effect of horse spleen ferritin (HFR) on the production of superox ide anion (O-2(.-)) by equine blood monocytes was investigated. Preinc ubation of monocytes with HFR resulted in pronounced inhibition of O-2 (.-) 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 obs erved after preincubation of monocytes with HFR (2 mg/ml) for 18 h bef ore stimulation with PMA. ApoHFR at the same concentration showed only about one-third of the inhibitory effect of iron-saturated HFR. Vario us iron complexes, such as iron dextran, hemin, or ferric ammonium sul fate, had no significant effect on O-2(.-) production by monocytes. Ne ither catalase (Cat) nor desferrioxamine (DFO) changed the inhibitory effect of HFR. These findings suggest that HFR may play an important r ole in inhibition of superoxide generation by equine monocytes. Althou gh the mechanism of this inhibition remains unknown, the results obtai ned suggest that it is not due to ferritin-dependent oxidative inactiv ation of the NADPH-oxidase system in stimulated monocytes.