Trafficking of Endogenous Immunoglobulins by Endothelial Cells at the Blood-Brain Barrier.
Fiche publication
Date publication
mai 2016
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Mme MESSADDEQ Nadia
Tous les auteurs :
Villaseñor R, Ozmen L, Messaddeq N, Grüninger F, Loetscher H, Keller A, Betsholtz C, Freskgård PO, Collin L
Lien Pubmed
Résumé
The Blood-Brain Barrier (BBB) restricts access of large molecules to the brain. The low endocytic activity of brain endothelial cells (BECs) is believed to limit delivery of immunoglobulins (IgG) to the brain parenchyma. Here, we report that endogenous mouse IgG are localized within intracellular vesicles at steady state in BECs in vivo. Using high-resolution quantitative microscopy, we found a fraction of endocytosed IgG in lysosomes. We observed that loss of pericytes (key components of the BBB) in pdgf-b(ret/ret) mice affects the intracellular distribution of endogenous mouse IgG in BECs. In these mice, endogenous IgG was not detected within lysosomes but instead accumulate at the basement membrane and brain parenchyma. Such IgG accumulation could be due to reduced lysosomal clearance and increased sorting to the abluminal membrane of BECs. Our results suggest that, in addition to low uptake from circulation, IgG lysosomal degradation may be a downstream mechanism by which BECs further restrict IgG access to the brain.
Mots clés
Animals, Blood-Brain Barrier, metabolism, Endothelial Cells, metabolism, Immunoglobulin G, Immunoglobulins, metabolism, Intracellular Space, metabolism, Lysosomes, metabolism, Mice, Pericytes, metabolism, Phosphorylation, tau Proteins, metabolism
Référence
Sci Rep. 2016 05 6;6:25658