title: Non-transferrin-bound iron (NTBI) uptake by T lymphocytes: evidence for the selective acquisition of oligomeric ferric citrate species.
abstract: 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.
authors.affiliation: Basic and Clinical Research on Iron Biology, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Joao
authors.initials: J
authors.lastname: Arezes
authors.forename: Monica
authors.initials: M
authors.lastname: Costa
authors.forename: Ines
authors.initials: I
authors.lastname: Vieira
authors.forename: Vera
authors.initials: V
authors.lastname: Dias
authors.forename: Xiao L
authors.initials: XL
authors.lastname: Kong
authors.forename: Rui
authors.initials: R
authors.lastname: Fernandes
authors.forename: Matthijn
authors.initials: M
authors.lastname: Vos
authors.forename: Anna
authors.initials: A
authors.lastname: Carlsson
authors.forename: Yuri
authors.initials: Y
authors.lastname: Rikers
authors.forename: Graça
authors.initials: G
authors.lastname: Porto
authors.forename: Maria
authors.initials: M
authors.lastname: Rangel
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
authors.forename: Jorge P
authors.initials: JP
authors.lastname: Pinto
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology; D005290:Ferric Compounds / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D005290:Ferric Compounds; C025314:ferric citrate; D007501:Iron