title: Alterations in tight junction protein and IgG permeability accompany leukocyte extravasation across the choroid plexus during neuroinflammation.
abstract: The choroid plexus (CP) is considered to be a point of leukocyte entry into the CNS during normal immune surveillance and in neuroinflammatory diseases. The structural and functional alterations within the CP that support this migration are not understood. We used quantitative, high-resolution, 3-dimensional (3-D) fluorescence imaging to analyze CP alterations associated with inflammatory responses in C57/Bl6 mice after the induction of experimental autoimmune encephalomyelitis by immunization with myelin oligodendrocyte glycoprotein (MOG) and complete Freund adjuvant/pertussis toxin (MOG-CFA/PTX) or adjuvants alone (CFA-PTX). The MOG-CFA/PTX and CFA/PTX produced similar effects, although those caused by the former were consistently more marked. Both treatments resulted in the accumulation of serum immunoglobulin G and leukocytes in the CP stroma, consistent with elevated stromal capillary permeability. They also provoked distortions and diminished immunostaining patterns of the tight junction adaptor protein ZO-1 in the choroidal epithelium but no obvious change in the patterns of the tight junction associated protein claudin-2. Only MOG-CFA/PTX triggered visible extravasation of immunoglobulin G and leukocytes across the choroidal epithelium. Our results suggest that CFA/PTX primes the CP for neuroinflammation by inducing structural changes that are exacerbated when there is an immune response to MOG and reinforce the CP as a gateway for leukocytes to enter the CNS by accessing the CSF and leptomeninges.
authors.affiliation: From the Blood-Brain Barrier Laboratory, Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut.
authors.forename: Bandana
authors.initials: B
authors.lastname: Shrestha
authors.forename: Debayon
authors.initials: D
authors.lastname: Paul
authors.forename: Joel S
authors.initials: JS
authors.lastname: Pachter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D002831:Choroid Plexus / Q000276:immunology / Q000378:metabolism*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D062725:Tight Junction Proteins / Q000276:immunology / Q000378:metabolism*; D019108:Tight Junctions / Q000276:immunology / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; D018836:Inflammation Mediators; D062725:Tight Junction Proteins