EFFECT OF HEPATIC ISOFERRITINS FROM IRON-OVERLOADED RATS ON LYMPHOCYTE PROLIFERATIVE RESPONSE - ROLE OF FERRITIN IRON CONTENT

Iron and ferritin impair a variety of immunological functions. To eval uate the effect of ferritin iron content on rat lymphocyte proliferati ve response, isoferritins that differ in their iron content and isoele ctric point (pI) were isolated from iron overload rat livers by ultrac entrifugation (isoferritins with high iron content and low pI) or crys tallization (isoferritins with low iron content and high pI) methods. Additionally, commercial horse splenic ferritin (with a lower pI and h igher iron content than rat isoferritins) was also tested. Proliferati ve response to Con A was decreased in a dose-dependent manner in all a ssays in which spleen cells were incubated with rat and horse isoferri tins. However, isoferritins with higher iron contents (rat isoferritin obtained by ultracentrifugation and horse ferritin) caused a greater decrease of proliferative response at 5 and 25 mu g/ml than the others . Rat and horse apoferritins showed no inhibitory effect on lymphocyte proliferative response, suggesting that the effect is due to iron pro bably through the damaging effect of reactive oxygen species generated by iron released by the isoferritins on lymphocyte functions. Additio nally, the role of serum ferritin level on proliferative response was studied in an experimental model of iron overload in rats. An inverse relationship between the proliferative response and serum ferritin lev els was observed.Our results suggest that the inhibitory effect of the isoferritins on lymphocyte proliferative response is due, at least pa rtially, to the iron content of this protein and not exclusively to va riation in pI as suggested by other authors. These results are in agre ement with the possible immunosuppressor role of ferritin in vivo.