Receptor‐mediated transcytosis of transferrin across the blood‐brain barrier

Abstract

The perfusion of rat brain with 125I-transferrin resulted in a receptor-mediated uptake of transferrin into the endothelium of the blood-brain barrier followed by its detection in the brain. During a pulse-chase experiment, 125I-transferrin accumulated in the endothelial cells during the pulse, with a decrease of this intraendothelial radioactivity during the chase associated with a concomitant increase in the nonvascular elements of the brain. The receptor-mediated movement of transferrin across the blood-brain barrier suggests that the brain may derive its iron through the transcytosis of iron-loaded transferrin across the brain microvasculature. We discuss the likelihood that aluminum and other potentially toxic heavy metals, which also bind tightly to transferrin, may enter the brain by this pathway. We also discuss the possibility that other large molecules including neuroactive peptides and neurotrophic viruses may enter the brain through a similar receptor-mediated, vesicular transcytotic route.

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

“…This result, together with the presence of a transferrin-mediated vesicle-based transcytosis system through the BBB [19,20,48,49] makes HFt-based NCs potentially good carriers for toxic molecules to the brain tumors.…”

Delivery of drugs, proteins and genes into cells using transferrin as a ligand for receptor-mediated endocytosis

“…Jefferies and colleagues [91] discovered that after injection into the blood, monoclonal antibodies against the TfR labeled the endothelium of brain capillaries but not of other tissues. Further studies showed binding, endocytosis and transcytosis of iodine-labeled Tf by brain capillaries [92,93]. Only 20% of Tf was found to be recycled whereas approximately 50% was transcytosed into the brain parenchyma.…”

Manganese neurotoxicity: A focus on the neonate

“…Since Tf receptors are present on the surface of the cerebral capillaries (Fishman et al, 1985;Jeffries et al, 1984;Partridge et al, 1987) and endocytosis of Tf is known to occur in these capillaries (Partridge et al, 1987), it has been suggested that Mn (in the trivalent oxidation state) enters the endothelial cells complexed with Tf. Mn is then released from the complex in the endothelial cell interior by endosomal acidification and the apo-Tf Tf complex is returned to the luminal surface (Morris et al, 1992a;Morris et al, 1992b) without the assistance of DMT1 (Divalent Metal Transporter-1) (Moos et al, 2006).…”