Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier

Carine Fillebeen 1 Laurence Descamps 2 Marie-Pierre Dehouck 3 Laurence Fenart 3 Monique Benaissa 1 Geneviève Spik 1 Roméo Cecchelli 3 Annick Pierce 1
1 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
2 Pharmacocinétique et Métabolisme Préclinique
3 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique
Abstract : 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.
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Contributor : Wilfried Déplanques <>
Submitted on : Wednesday, November 3, 2010 - 4:34:36 PM
Last modification on : Tuesday, July 3, 2018 - 11:21:27 AM

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Carine Fillebeen, Laurence Descamps, Marie-Pierre Dehouck, Laurence Fenart, Monique Benaissa, et al.. Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 1999, 274 (11), p. 7011-7017. ⟨hal-00531751⟩

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