Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme.
In the central nervous system (CNS) complex endothelial tight junctions (TJs) form a restrictive paracellular diffusion barrier, the blood-brain barrier (BBB). During inflammation, BBB properties are frequently lost, resulting in brain edema. To investigate whether BBB leakiness correlates with molecular changes at BBB TJs, we performed immunofluorescence stainings for TJ molecules in a mouse model of experimental autoimmune encephalomyelitis (EAE) and in human tissue with glioblastoma multiforme (GBM). In TJs of healthy CNS vessels in both mouse and man we detected occludin, ZO-1, claudin-5 and claudin-3. In EAE brain and spinal cord sections we observed the selective loss of claudin-3 immunostaining from TJs of venules surrounded by inflammatory cuffs, whereas the localization of the other TJ proteins remained unchanged. In addition, selective loss of claudin-3 immunostaining was also observed in altered cerebral microvessels of human GBM. Our data demonstrate the selective loss of claudin-3 from BBB TJs under pathological conditions such as EAE or GBM when the integrity of the BBB is compromised, and therefore suggest that claudin-3 is a central component determining the integrity of BBB TJs in vivo.
Wolburg
Hartwig
H
Institute for Pathology, University of Tübingen, Liebermeisterstrasse 8, 72076, Tübingen, Germany. hartwig.wolburg@med.uni-tuebingen.de
Wolburg-Buchholz
Karen
K
Kraus
Jörg
J
Rascher-Eggstein
Gesa
G
Liebner
Stefan
S
Hamm
Stefan
S
Duffner
Frank
F
Grote
Ernst-H
EH
Risau
Werner
W
Engelhardt
Britta
B
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D062465:Claudin-3; D062507:Claudin-5; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism* / Q000473:pathology; D062826:Zonula Occludens-1 Protein
C568122:CLDN3 protein, human; C107466:CLDN5 protein, human; D062465:Claudin-3; D062507:Claudin-5; C568123:Cldn3 protein, mouse; C491511:Cldn5 protein, mouse; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein