ppat.1008014.g002.tif (3.53 MB)
Epsilon toxin binds to the microvasculature of the CNS and requires expression of MAL.
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posted on 2019-11-08, 18:34 authored by Jennifer R. Linden, Claudia Flores, Eric F. Schmidt, Francisco A. Uzal, Adam O. Michel, Marissa Valenzuela, Sebastian Dobrow, Timothy VartanianWild type mice expressing Mal+/+ or mice deficient in Mal-/- were intravenously injected with Alexa Fluor 594 conjugated ETX (ETX-594) for ten minutes then perfused with PBS to remove unbound toxin. ETX binding to microvasculature was evaluated in brain or spinal cord cryosections and whole mounts of retina and optic nerve. FITC-BSL1 was used to identify microvasculature. ETX-594 bound to the microvasculature of the brain including areas near the corpus callosum (white-dotted line) and the cerebellum (white matter tracts denoted by white line, WM) as well as the spinal cord (thoracic segment), retina and optic nerve (full thickness of optic nerve denoted by white dashed lines). ETX-594 binding was not detected in Mal-/- mice.
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RABMAL Clostridium perfringens epsilon toxinClostridium perfringens epsilon toxinendosomeEEAInternalized caveolae fuselipid raft-dependent vacuolation60 kDA serum albumin155 kDA IgGmultivesicular bodies fuse basallyCNS microvasculaturecaveolae-dependent transcytosisETX causes blood brain barrier70 kDa dextranETX causes BBB permeability376 Da fluorescein saltETX bindingmultivesicular bodiesblood brain barrier permeabilityETX-induced BBB permeabilityexhibit ETX-induced BBB permeability
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