Non-transferrin-bound iron (NTBI) uptake by T lymphocytes: evidence for the selective acquisition of oligomeric ferric citrate species

• Published in: PloS one Vol. 8; no. 11; p. e79870
• Main Authors: Arezes, Joao, Costa, Monica, Vieira, Ines, Dias, Vera, Kong, Xiao L, Fernandes, Rui, Vos, Matthijn, Carlsson, Anna, Rikers, Yuri, Porto, Graça, Rangel, Maria, Hider, Robert C, Pinto, Jorge P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.11.2013; Public Library of Science (PLoS)
• Subjects: Analysis; Animal behavior; Biological activity; Biology; Blood & organ donations; Cardiomyopathy; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - metabolism; Cell division; Cells, Cultured; Chelating agents; Citric acid; Deoxyribonucleic acid; Disorders; DNA; DNA biosynthesis; Endocytosis - physiology; Erythropoiesis; Ferric citrate; Ferric Compounds - metabolism; Hep G2 Cells; Hepatocytes; Hepatocytes - metabolism; Hepatology; Hospitals; Humans; Immunoglobulins; Iron; Iron - metabolism; Kinetics; Low molecular weights; Lymphocytes; Lymphocytes T; Molecular weight; Nutrient transport; Oxygen; Pharmaceutical sciences; Plasma; Rodents; T-Lymphocytes - metabolism; Toxicity; Transferrin; Wireless communications services; Portugal
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0079870

Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI). NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.