IRON UPTAKE IN BLOOD-BRAIN-BARRIER ENDOTHELIAL-CELLS CULTURED IN IRON-DEPLETED AND IRON-ENRICHED MEDIA

Iron is essential in the cellular metabolism of all mammalian tissues, including the brain. Intracerebral iron concentrations vary with age and in several (neurological) diseases. Although it is evident that en dothelial cells lining the capillaries in the brain are of importance, factors governing the regulation of intracerebral iron concentration are unknown. To investigate the role of blood-brain barrier endothelia l cells in cerebral iron regulation, primary cultures of porcine blood -brain barrier endothelial cells were grown in either iron-enriched or iron-depleted medium. Iron-enriched cells showed a reduction in surfa ce-bound and total transferrin receptor numbers compared with iron-dep leted cells. Transferrin receptor kinetics showed that the transferrin receptor internalization rate in iron-enriched cultures was higher, w hereas the transferrin receptor externalization rate in iron-enriched cultures was lower than the rate in iron-depleted cultures. Moreover, blood-brain barrier endothelial cells cultured in iron-enriched medium were able to accumulate more iron intracellularly, which underlines o ur kinetic data on transferrin receptors. Our results agree with histo pathological studies on brain tissue of patients with hemochromatosis, suggesting that at high peripheral iron concentrations, the rate of i ron transport across the blood-brain barrier endothelial cells is to s ome extent proportional to the peripheral iron concentration.