Macrophage erythrophagocytosis and iron exocytosis

Senescent, or damaged, erythrocytes are removed from the blood stream mainly by the macrophage system. Such cells may acquire and store large quantities of the redox-active transition metal iron that, if released together with superoxide and hydrogen peroxide during an oxidative burst, may induce peroxidative reactions with a variety of surrounding substances, e.g., low-density lipoprotein (LDL). In this study we demonstrate 1. the temporary sequestration of iron within the secondary lysosomal apparatus of both established macrophage-like J-774 cells and human monocyte-derived macrophages secondary to the uptake and degradation of native and photo-oxidized (ultraviolet UV light) erythrocytes; and 2. an ensuing development by these cells of a capacity for iron-exocytosis. The binding and uptake by human macrophages and J-774 cells of artificially aged, UV-irradiated erythrocytes were stimulated compared to that of native erythrocytes. The uptake resulted in lysosomal accumulation of iron in a low-molecular weight form, as shown by autometallography. Cells exposed to ferric chloride were used as positive controls. Ensuing exocytosis of iron to the culture medium was demonstrated by atomic absorption spectroscopy. Our findings suggest that macrophage erythrophagocytosis is a useful model for the study of the sequestration of iron within the macrophage acidic vacuolar apparatus, its subsequent exocytosis, and oxidative effect on extracellular LDL.