The nature of iron released by resident and stimulated mouse peritoneal macrophages

Mouse peritoneal macrophages were allowed to ingest ⁵⁹Fe, ¹²⁵I-labelled transferrin-antitransferrin immune complexes, and the release of ⁵⁹Fe and degraded transferrin was studied. Some iron was released as ferritin, but a major portion was bound by bovine transferrin present in the culture medium, which contained fetal calf serum. If the medium was saturated with iron prior to incubation with the cells, little of the released iron was then bound by transferrin but appeared either as a high molecular weight fraction or, if nitrilotriacetate was present in the medium, some also appeared as a low molecular weight fraction. The release of non-ferritin iron was biphasic, the early, rapid phase being more prolonged with resident cells than with stimulated cells. The rate of release in the late phase did not differ significantly between resident and stimulated cells. Incubation at 0°C completely suppressed the release of degraded transferrin, but iron release continued at about 30% of the rate seen in control cultures at 37°C. A model for the intracellular handling of ingested iron is proposed to take account of the different release patterns of resident and stimulated macrophages.