Immunological properties of ferritin during in vitro maturation of human monocytes

Ferritin in macrophages from human liver and spleen is rich in L subunits but, in the peripheral blood monocytes from which tissue macrophages are derived, the ferritin contains a high proportion of H subunits. We have studied the maturation of monocytes in vitro and the immunological properties of cellular ferritin during this process. Mononuclear cells were isolated from peripheral blood of normal subjects and patients with idiopathic haemochromatosis. Monocytes were obtained by incubation on plastic. The adherent cells were incubated in medium with or without added iron (ferric ammonium citrate) for 20 hours and harvested. Monocytes were also incubated for 7 days before incubation with iron. Ferritin concentrations were determined using immunoassays specific for H and L rich isoferritins. Freshly isolated monocytes were found to have similar concentrations of H- and L-rich isoferritins. Incubation with iron caused an increase in both H- and L-type ferritins. After incubation for 7 d the ferritin present in the normal cell lysates was L-rich and incubation with iron caused accumulation of L-, but not H-type ferritin. Maturation of monocytes is thus associated with the loss of H-rich isoferritins. There were no differences between normal subjects and patients with idiopathic haemochromatosis in ferritin concentrations. In vitro maturation provides an excellent model for studying the developmental control of ferritin synthesis and breakdown.