Transport of cationized anti-tetanus Fab'2 fragments across an in vitro blood-brain barrier model: involvement of the transcytosis pathway

Julie Girod Laurence Fenart 1 Anthony Régina Marie-Pierre Dehouck 1 Guying Hong Jean-Michel Scherrmann 2 Roméo Cecchelli 1 Françoise Roux 2
1 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique
2 NAVVEC (UM 81) - Neuropsychopharmacologie des addictions. Vulnérabilité et variabilité expérimentale et clinique
Abstract : Tetanus neurotoxin reaches the CNS by axonal retrograde transport and thus becomes inaccessible to current treatments. A possible strategy to improve current therapy for tetanus disease would be the vectorization of Fab'2 fragments, allowing their delivery into the CNS. The purpose of this study was to investigate whether after cationization anti-tetanus Fab'2 fragments are able to cross the blood–brain barrier, the first obstacle to CNS delivery. We used primary cocultures of bovine brain capillary endothelial cells and newborn rat astrocytes as an in vitro model to study the binding and transport of cationized Fab'2 (cFab'2) fragments across the brain endothelium. We first show that cationization does not alter Fab'2 affinity for tetanus toxin. Then we demonstrate that after cationization Fab'2 fragments are able to bind to the negative charges on the surface of endothelial cells and subsequently to be transported across the endothelial cell monolayer without any modification of affinity. Finally, using fluorescence microscopy, we show that cFab'2 fragments are transported through endocytotic vesicles. The present study demonstrates that cationization allows Fab'2 directed against tetanus toxin to be transported through brain endothelium by adsorptive-mediated transcytosis. We suggest that this vectorization way could be a promising delivery strategy for carrying anti-tetanic immunoglobulin fragments across the blood–brain barrier to improve tetanus treatment.
Keywords : Brain capillary endothelial cells Tetanus toxin Cationization Transcytosis
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Article dans une revue
Journal of Neurochemistry, Wiley, 1999, 73 (5), p. 2002-2008
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Soumis le : lundi 11 octobre 2010 - 13:51:10
Dernière modification le : jeudi 15 novembre 2018 - 20:27:16

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Julie Girod, Laurence Fenart, Anthony Régina, Marie-Pierre Dehouck, Guying Hong, et al.. Transport of cationized anti-tetanus Fab'2 fragments across an in vitro blood-brain barrier model: involvement of the transcytosis pathway. Journal of Neurochemistry, Wiley, 1999, 73 (5), p. 2002-2008. 〈hal-00525208〉

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