Trafficking of Endogenous Immunoglobulins by Endothelial Cells at the Blood-Brain Barrier

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 ve...

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Published inScientific reports Vol. 6; no. 1; p. 25658
Main Authors Villaseñor, Roberto, Ozmen, Laurence, Messaddeq, Nadia, Grüninger, Fiona, Loetscher, Hansruedi, Keller, Annika, Betsholtz, Christer, Freskgård, Per-Ola, Collin, Ludovic
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 06.05.2016
Subjects
Animals
Biochemistry, Molecular Biology
Blood-brain barrier
Blood-Brain Barrier - metabolism
Blood-Brain Barrier - ultrastructure
Endothelial cells
Endothelial Cells - metabolism
Immunoglobulin G
Immunoglobulins
Immunoglobulins - metabolism
Intracellular
Intracellular Space - metabolism
Life Sciences
Lysosomes
Lysosomes - metabolism
Lysosomes - ultrastructure
Medicin och hälsovetenskap
Mice
Parenchyma
Pericytes
Pericytes - metabolism
Pericytes - ultrastructure
Phosphorylation
tau Proteins - metabolism
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Summary: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.
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PMCID: PMC4858719
ISSN:2045-2322
2045-2322
DOI:10.1038/srep25658