Effects of isoferritins on human granulocytes

Serum ferritin levels are often elevated in patients with certain cancers and these elevations are, in part, derived from the tumors. In such patients, the increased levels of serum ferritin are associated with a poor prognosis. This association may be explained in part by biological effects of ferritin on lymphocytes: inhibition of E-rosette formation, masking of cell surfaces and suppression of lymphocytes' response to mitogens in vitro. The authors hypothesized that ferritins from tumor tissues also exert adverse effects on human granulocytes that are involved in tumoricidal activity. Three granulocyte functions were tested: nitroblue tetrazolium test, phagocytosis, and production of hydrogen peroxide. The results supported the authors' hypothesis: NBT reduction and phagocytosis are decreased in granulocytes exposed to ferritins, more so with tumor ferritins, than normal ferritin, and H2O2 production is less in granulocytes previously exposed to ferritins from tumor and nontumor tissues than cells not exposed to ferritins. However, the inhibitory effects of ferritins on H2O2 production can be reversed if granulocytes are further stimulated by phorbol myristate acetate (a membrane stimulant). If the elevated serum ferritin in cancer patients impairs granulocyte functions, in vivo, then it may increase the risk of infection, decrease tumoricidal host responses, and, thereby, contribute to the poor prognosis of these individuals.