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Receptor-mediated Transcytosis of Lactoferrin through the Blood-Brain Barrier

Lactoferrin (Lf) is an iron-binding protein involved in host defense against infection and severe inflammation; it accumulates in the brain during neurodegenerative disorders. Before determining Lf function in brain tissue, we investigated its origin and demonstrate here that it crosses the blood-br...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-03, Vol.274 (11), p.7011-7017
Main Authors: Fillebeen, Carine, Descamps, Laurence, Dehouck, Marie-Pierre, Fenart, Laurence, Benaı̈ssa, Monique, Spik, Geneviève, Cecchelli, Roméo, Pierce, Annick
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Language:English
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Summary:Lactoferrin (Lf) is an iron-binding protein involved in host defense against infection and severe inflammation; it accumulates in the brain during neurodegenerative disorders. Before determining Lf function in brain tissue, we investigated its origin and demonstrate here that it crosses the blood-brain barrier. An in vitro model of the blood-brain barrier was used to examine the mechanism of Lf transport to the brain. We report that differentiated bovine brain capillary endothelial cells exhibited specific high (Kd = 37.5 nm; n = 90,000/cell) and low (Kd = 2 μm;n = 900,000 sites/cell) affinity binding sites. Only the latter were present on nondifferentiated cells. The surface-bound Lf was internalized only by the differentiated cell population leading to the conclusion that Lf receptors were acquired during cell differentiation. A specific unidirectional transport then occurred via a receptor-mediated process with no apparent intraendothelial degradation. We further report that iron may cross the bovine brain capillary endothelial cells as a complex with Lf. Finally, we show that the low density lipoprotein receptor-related protein might be involved in this process because its specific antagonist, the receptor-associated protein, inhibits 70% of Lf transport.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.11.7011