Coincident expression and distribution of melanotransferrin and transferrin receptor in human brain capillary endothelium

• Published in: Brain research 1996-03, Vol.712 (1), p.117-121
• Main Authors: Rothenberger, Sylvia, Food, Michael R., Gabathuler, Reinhard, Kennard, Malcolm L., Yamada, Tatsuo, Yasuhara, Osamu, L. McGeer, Patrick, Jefferies, Wilfred A.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal; Antigens, Neoplasm - analysis; Antigens, Surface - analysis; Biological and medical sciences; Biological Transport - physiology; Blood brain barrier; Blood-Brain Barrier - physiology; Capillary endothelium; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; CHO Cells; Cricetinae; Fundamental and applied biological sciences. Psychology; Human brain; Humans; Iron - pharmacokinetics; Melanoma - immunology; Melanoma-Specific Antigens; Melanotransferrin; Neoplasm Proteins - analysis; Precipitin Tests; Receptors, Transferrin - analysis; Transferrin - analysis; Traosferrin receptor; Tumor Cells, Cultured; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(96)88505-2

One method of iron transport across the blood brain barrier (BBB) involves the transferrin receptor (TR), which is localized to the specialized brain capillary endothelium [7]. The melanotransferrin (MTf) molecule, also called p97, has been widely described as a melanoma specific molecule, however, its expression in brain tissues has not been addressed. MTf has a high level of sequence homology to transferrin (Tf) and lactoferrin, but is unusual because it predominantly occurs as a membrane bound, glycosylphosphatidylinositol (GPI) anchored molecule, but can also occur as a soluble form. We have recently demonstrated that GPI-anchored MTf provides a novel route for cellular iron uptake which is independent of Tf and its receptor [10]. Here we consider whether MTf may have a role in the transport of iron across the BBB. The distributions of MTf, Tf and the TR were studied immunohistochemically in human brain tissues. The distributions of MTf and TR were remarkably similar, and quite different from that of Tf. In all brain tissues examined, MTf and the TR were highly localized to capillary endothelium, while Tf itself was mainly localized to glial cells. These data suggest that MTf may play a role in iron transport within the human brain.