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

Villasenor, RobertoRoche Innovat Ctr Basel, Roche Pharma Res & Early Dev pRED, Neurodegenerat & Regenerat, Basel, Switzerland. (författare)

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.

Ozmen, LaurenceRoche Innovat Ctr Basel, Roche Pharma Res & Early Dev pRED, Neurodegenerat & Regenerat, Basel, Switzerland. (författare)
Messaddeq, NadiaUdS, Coll France, CNRS, IGBMC,INSERM,ICS, BP 10142, Strasbourg, France. (författare)
Gruninger, FionaRoche Innovat Ctr Basel, Roche Pharma Res & Early Dev pRED, Neurodegenerat & Regenerat, Basel, Switzerland. (författare)
Loetscher, HansruediRoche Innovat Ctr Basel, Roche Pharma Res & Early Dev pRED, Neurodegenerat & Regenerat, Basel, Switzerland. (författare)
Keller, AnnikaUniv Zurich, Univ Zurich Hosp, Div Neurosurg, Frauenklin Str 10, CH-8091 Zurich, Switzerland. (författare)
Betsholtz, ChristerKarolinska Institutet,Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden.(Swepub:uu)chbet517 (författare)
Freskgard, Per-OlaRoche Innovat Ctr Basel, Roche Pharma Res & Early Dev pRED, Neurodegenerat & Regenerat, Basel, Switzerland. (författare)
Collin, LudovicRoche Innovat Ctr Basel, Roche Pharma Res & Early Dev pRED, Neurodegenerat & Regenerat, Basel, Switzerland. (författare)
Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev pRED, Neurodegenerat & Regenerat, Basel, Switzerland.UdS, Coll France, CNRS, IGBMC,INSERM,ICS, BP 10142, Strasbourg, France. (creator_code:org_t)

Av författaren/redakt...: Villasenor, Robe ...; Ozmen, Laurence; Messaddeq, Nadia; Gruninger, Fiona; Loetscher, Hansr ...; Keller, Annika; visa fler...; Betsholtz, Chris ...; Freskgard, Per-O ...; Collin, Ludovic; visa färre...

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