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 evaluate the effect of ferritin iron content on rat lymphocyte proliferative response, isoferritins that differ in their iron content and isoelectric point (pI) were isolated from iron overload rat livers by ultracentrifugation (isoferritins with high iron content and low pI) or crystallization (isoferritins with low iron content and high pI) methods. Additionally, commercial horse splenic ferritin (with a lower pI and higher iron content than rat isoferritins) was also tested. Proliferative response to Con A was decreased in a dose-dependent manner in all assays in which spleen cells were incubated with rat and horse isoferritins. 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 micrograms/ml than the others. Rat and horse apoferritins showed no inhibitory effect on lymphocyte proliferative response, suggesting that the effect is due to iron probably through the damaging effect of reactive oxygen species generated by iron released by the isoferritins on lymphocyte functions. Additionally, 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 levels was observed. Our results suggest that the inhibitory effect of the isoferritins on lymphocyte proliferative response is due, at least partially, to the iron content of this protein and not exclusively to variation in pI as suggested by other authors. These results are in agreement with the possible immunosuppressor role of ferritin in vivo.