Interactions between isolated hepatocytes and kupffer cells in iron metabolism: A possible role for ferritin as an iron carrier protein

• Published in: Hepatology (Baltimore, Md.) Md.), 1988-03, Vol.8 (2), p.296-301
• Main Authors: Sibille, Jean‐Claude, Kondo, Hitoshi, Aisen, Philip
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carrier Proteins - physiology; Cell Separation; Cells, Cultured; Erythrocytes - physiology; Ferritins - metabolism; Ferritins - physiology; Fundamental and applied biological sciences. Psychology; Iron - metabolism; Iron-Binding Proteins; Kupffer Cells - metabolism; Kupffer Cells - physiology; Liver - cytology; Liver - metabolism; Liver - physiology; Liver. Bile. Biliary tracts; Phagocytosis; Transferrin-Binding Proteins; Vertebrates: digestive system
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.1840080218

Like the rat peritoneal macrophage, the isolated Kupffer cell is capable of processing and releasing iron acquired by phagocytosis of immunosensitized homologous red blood cells. When erythrophagocytosis is restrained to levels which do not affect cell viability, about one red cell per macrophage, close to 50% of iron acquired from red cells is released within 24 hr in the form of ferritin. Immunoradiometric assay of the extracellular medium indicates that 160 ng ferritin are released by 106 Kupffer cells after 24‐hr incubation at 37°C. Iron release is temperature‐dependent, the rate at 37°C being nearly 5‐fold greater than at 4°C. As estimated by sucrose‐gradient ultracentrifugation, ferritin released by the erythrophagocytosing Kupffer cell averages 2,400 iron atoms per molecule. When reincubated with isolated hepatocytes, this released ferritin is rapidly taken up by the cells. Via this process, hepatocytes may accumulate more than 160,000 iron atoms per cell per min. Such accumulation is not impeded by the presence of iron‐loaded transferrin in the culture medium, but is markedly depressed by rat liver ferritin. In contrast to the conservation of transferrin during its interaction with hepatocytes, the protein shell of the ferritin molecule is rapidly degraded into trichloroacetic acid‐soluble fragments. Ferritin‐mediated transfer of iron from Kupffer cells to hepatocytes may help explain the resistance of the liver to iron deficiency as well as the liver's susceptibility to iron overload.