Tumor necrosis factor-α increases lactoferrin transcytosis through the blood-brain barrier

Catherine Fillebeen Bénédicte Dehouck 1 Monique Benaïssa 2 Isabelle Dhennin-Duthille 2 Roméo Cecchelli 3 Annick Pierce 2
1 JPArc - U837 Inserm - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer
2 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
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, which accumulates in the brain during neurodegenerative disorders. Prior to determining Lf function in pathological brain tissues, we investigated its transport through the blood–brain barrier (BBB) in inflammatory conditions. For this purpose, we used a reconstituted BBB model consisting of the coculture of bovine brain capillary endothelial cells (BBCECs) and astrocytes in the presence of tumor necrosis factor-α (TNF-α). As TNF-α can be either synthesized by brain glial cells or present in circulating blood, BBCECs were exposed to this cytokine at their luminal or abluminal side. We have been able to demonstrate that in the presence of TNF-α, whatever the type of exposure, BBCECs were activated and Lf transport through the activated BBCECs was markedly increased. Lf was recovered intact at the abluminal side of the cells, suggesting that increased Lf accumulation may occur in immune-mediated pathophysiology. This process was transient as 20 h later, cells were in a resting state and Lf transendothelial traffic was back to normal. The enhancement of Lf transcytosis seems not to involve the up-regulation of the Lf receptor but rather an increase in the rate of transendothelial transport.
Keywords : Lactoferrin Blood–brain barrier Tumor necrosis factor-α Inflammation Neurodegenerative disorders Transendothelial transport
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Journal articles
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https://hal-univ-artois.archives-ouvertes.fr/hal-00525285
Contributor : Wilfried Déplanques <>
Submitted on : Monday, October 11, 2010 - 3:23:38 PM
Last modification on : Tuesday, July 3, 2018 - 11:28:56 AM

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Catherine Fillebeen, Bénédicte Dehouck, Monique Benaïssa, Isabelle Dhennin-Duthille, Roméo Cecchelli, et al.. Tumor necrosis factor-α increases lactoferrin transcytosis through the blood-brain barrier. Journal of Neurochemistry, Wiley, 1999, 73 (6), p. 2491-2500. ⟨hal-00525285⟩

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