Model of Reticuloendothelial Iron Metabolism in Humans: Abnormal Behavior in Idiopathic Hemochromatosis and in Inflammation

• Published in: Blood Vol. 74; no. 2; pp. 844 - 851
• Main Authors: Fillet, Georges, Beguin, Yves, Baldelli, Laurent
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.08.1989; The Americain Society of Hematology
• Subjects: 550501 - Metabolism- Tracer Techniques; 550901 - Pathology- Tracer Techniques; ANIMAL TISSUES; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; Biological and medical sciences; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BLOOD FORMATION; BLOOD PLASMA; BODY; BODY FLUIDS; DAYS LIVING RADIOISOTOPES; DISEASES; ELECTRON CAPTURE RADIOISOTOPES; ELEMENTS; ENERGY; ERYTHROCYTES; Erythrocytes, Abnormal - metabolism; Erythrocytes, Abnormal - pathology; ERYTHROPOIESIS; EVEN-ODD NUCLEI; GLOBULINS; GLOBULINS-BETA; HEAT; HEMIC DISEASES; Hemochromatosis - blood; Hemochromatosis - metabolism; Hemochromatosis - pathology; Hot Temperature; Humans; Hyperplasia; INFLAMMATION; INTERMEDIATE MASS NUCLEI; IRON; Iron - blood; Iron - metabolism; IRON 55; IRON 59; IRON ISOTOPES; Iron Radioisotopes - metabolism; ISOTOPE APPLICATIONS; ISOTOPES; Kinetics; Male; MATERIALS; Medical sciences; MEMBRANE TRANSPORT; Metabolic diseases; METABOLISM; METALLOPROTEINS; METALS; Metals (hemochromatosis...); Mononuclear Phagocyte System - metabolism; Mononuclear Phagocyte System - pathology; NUCLEI; ORGANIC COMPOUNDS; Other metabolic disorders; PATHOGENESIS; PATHOLOGICAL CHANGES; PATIENTS; PROTEINS; RADIOISOTOPES; Red-Cell Aplasia, Pure - blood; Red-Cell Aplasia, Pure - metabolism; RETICULOENDOTHELIAL SYSTEM; SYMPTOMS; TISSUES; TRACER TECHNIQUES; TRANSFERRIN; TRANSITION ELEMENTS; YEARS LIVING RADIOISOTOPES; Human; Hemochromatosis; Reticuloendothelial system; Idiopathic; Ion transport; Metabolic diseases; Iron; Inflammation; Metabolism; Inorganic element; Blood; Regulation(control); Pigments; Serum
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V74.2.844.844

Iron transport in the reticuloendothelial (RE) system plays a central role in iron metabolism, but its regulation has not been characterized physiologically in vivo in humans. In particular, why serum iron is elevated and RE cells are much less iron-loaded than parenchymal cells in idiopathic hemochromatosis is not known. The processing of erythrocyte iron by the RE system was studied after intravenous (IV) injection of 59Fe heat-damaged RBCs (HDRBCs) and 55Fe transferrin in normal subjects and in patients with iron deficiency, idiopathic hemochromatosis, inflammation, marrow aplasia, or hyperplastic erythropoiesis. Early release of 59Fe by the RE system was calculated from the plasma iron turnover and the 59Fe plasma reappearance curve. Late release was calculated from the ratio of 59Fe/ 55Fe RBC utilization in 2 weeks. The partitioning of iron between the early (release from heme catabolism) and late (release from RE stores) phases depended on the size of RE iron stores, as illustrated by the inverse relationship observed between early release and plasma ferritin [P ≪ .001). There was a strong correlation between early release and the rate of change of serum iron levels during the first three hours in normal subjects (r = .85, P ≪ .001). Inflammation produced a blockade of the early release phase, whereas in idiopathic hemochromatosis early release was considerably increased as compared with subjects with similar iron stores. Based on these results, we describe a model of RE iron metabolism in humans. We conclude that the RE system appears to determine the diurnal fluctuations in serum iron levels through variations in the immediate output of heme iron. In idiopathic hemochromatosis, a defect of the RE cell in withholding iron freed from hemoglobin could be responsible for the high serum iron levels and low RE iron stores. © 1989 by Grune & Stratton. Inc.