ABSTRACT
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.
Subject(s)
Ferritins/pharmacology , Granulocytes/drug effects , Granulocytes/metabolism , Humans , Hydrogen Peroxide/biosynthesis , In Vitro Techniques , Nitroblue Tetrazolium , Oxidation-Reduction , Phagocytosis/drug effects , Reference Values , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
The leukocyte migration inhibition assay has been widely used as an in vitro test cell mediated immunity to various substances. Using a leukemic cell line (RPMI 8402) as the source of antigen, we assayed leukocyte migration inhibition in seven children with acute lymphocytic leukemic (ALL), their family members (14 patients and 13 siblings), and 17 healthy adult controls. In six families, the patients showed stronger inhibition than their family members or controls. The patients differed significantly from their family members (P = 0.003) and all other persons without leukemia (P = 0.02). These results suggest that patients with ALL have developed a specific cellular immune reactivity to an antigen or antigens on leukemic cells, while their family members have not.
