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- W2987851504 endingPage "e1008014" @default.
- W2987851504 startingPage "e1008014" @default.
- W2987851504 abstract "Clostridium perfringens epsilon toxin (ETX) is responsible for causing the economically devastating disease, enterotoxaemia, in livestock. It is well accepted that ETX causes blood brain barrier (BBB) permeability, however the mechanisms involved in this process are not well understood. Using in vivo and in vitro methods, we determined that ETX causes BBB permeability in mice by increasing caveolae-dependent transcytosis in brain endothelial cells. When mice are intravenously injected with ETX, robust ETX binding is observed in the microvasculature of the central nervous system (CNS) with limited to no binding observed in the vasculature of peripheral organs, indicating that ETX specifically targets CNS endothelial cells. ETX binding to CNS microvasculature is dependent on MAL expression, as ETX binding to CNS microvasculature of MAL-deficient mice was not detected. ETX treatment also induces extravasation of molecular tracers including 376Da fluorescein salt, 60kDA serum albumin, 70kDa dextran, and 155kDA IgG. Importantly, ETX-induced BBB permeability requires expression of both MAL and caveolin-1, as mice deficient in MAL or caveolin-1 did not exhibit ETX-induced BBB permeability. Examination of primary murine brain endothelial cells revealed an increase in caveolae in ETX-treated cells, resulting in dynamin and lipid raft-dependent vacuolation without cell death. ETX-treatment also results in a rapid loss of EEA1 positive early endosomes and accumulation of large, RAB7-positive late endosomes and multivesicular bodies. Based on these results, we hypothesize that ETX binds to MAL on the apical surface of brain endothelial cells, causing recruitment of caveolin-1, triggering caveolae formation and internalization. Internalized caveolae fuse with early endosomes which traffic to late endosomes and multivesicular bodies. We believe that these multivesicular bodies fuse basally, releasing their contents into the brain parenchyma." @default.
- W2987851504 created "2019-11-22" @default.
- W2987851504 creator A5008162678 @default.
- W2987851504 creator A5024846892 @default.
- W2987851504 creator A5047683626 @default.
- W2987851504 creator A5058156831 @default.
- W2987851504 creator A5068705235 @default.
- W2987851504 creator A5076043581 @default.
- W2987851504 creator A5080893700 @default.
- W2987851504 creator A5081465627 @default.
- W2987851504 date "2019-11-08" @default.
- W2987851504 modified "2023-09-25" @default.
- W2987851504 title "Clostridium perfringens epsilon toxin induces blood brain barrier permeability via caveolae-dependent transcytosis and requires expression of MAL" @default.
- W2987851504 cites W1506045573 @default.
- W2987851504 cites W1549213315 @default.
- W2987851504 cites W1561024000 @default.
- W2987851504 cites W1579469490 @default.
- W2987851504 cites W1600104800 @default.
- W2987851504 cites W1621672474 @default.
- W2987851504 cites W1796054280 @default.
- W2987851504 cites W1799444595 @default.
- W2987851504 cites W1847021296 @default.
- W2987851504 cites W1852676216 @default.
- W2987851504 cites W1871259164 @default.
- W2987851504 cites W1929386789 @default.
- W2987851504 cites W1967606788 @default.
- W2987851504 cites W1969209049 @default.
- W2987851504 cites W1972173644 @default.
- W2987851504 cites W1972731882 @default.
- W2987851504 cites W1975954833 @default.
- W2987851504 cites W1979254764 @default.
- W2987851504 cites W1981913963 @default.
- W2987851504 cites W1983537174 @default.
- W2987851504 cites W1984561439 @default.
- W2987851504 cites W1985318723 @default.
- W2987851504 cites W1985455477 @default.
- W2987851504 cites W1987270140 @default.
- W2987851504 cites W1992070708 @default.
- W2987851504 cites W1992758695 @default.
- W2987851504 cites W1995763269 @default.
- W2987851504 cites W1996219643 @default.
- W2987851504 cites W1996574563 @default.
- W2987851504 cites W1996605553 @default.
- W2987851504 cites W1997010751 @default.
- W2987851504 cites W2000441131 @default.
- W2987851504 cites W2000852812 @default.
- W2987851504 cites W2001437044 @default.
- W2987851504 cites W2003717036 @default.
- W2987851504 cites W2012623954 @default.
- W2987851504 cites W2015541518 @default.
- W2987851504 cites W2015822750 @default.
- W2987851504 cites W2018707916 @default.
- W2987851504 cites W2019862207 @default.
- W2987851504 cites W2029248129 @default.
- W2987851504 cites W2030727312 @default.
- W2987851504 cites W2031704987 @default.
- W2987851504 cites W2032307055 @default.
- W2987851504 cites W2034742219 @default.
- W2987851504 cites W2035978552 @default.
- W2987851504 cites W2036821782 @default.
- W2987851504 cites W2039401375 @default.
- W2987851504 cites W2044565737 @default.
- W2987851504 cites W2046777097 @default.
- W2987851504 cites W2050291058 @default.
- W2987851504 cites W2053181243 @default.
- W2987851504 cites W2054275187 @default.
- W2987851504 cites W2057824725 @default.
- W2987851504 cites W2060334268 @default.
- W2987851504 cites W2062478419 @default.
- W2987851504 cites W2062840925 @default.
- W2987851504 cites W2063501528 @default.
- W2987851504 cites W2065436572 @default.
- W2987851504 cites W2074836708 @default.
- W2987851504 cites W2075922784 @default.
- W2987851504 cites W2080848411 @default.
- W2987851504 cites W2082004477 @default.
- W2987851504 cites W2084369099 @default.
- W2987851504 cites W2086047770 @default.
- W2987851504 cites W2087222747 @default.
- W2987851504 cites W2095024221 @default.
- W2987851504 cites W2095116102 @default.
- W2987851504 cites W2101700662 @default.
- W2987851504 cites W2101716445 @default.
- W2987851504 cites W2103548057 @default.
- W2987851504 cites W2104567497 @default.
- W2987851504 cites W2106303836 @default.
- W2987851504 cites W2108198962 @default.
- W2987851504 cites W2115155255 @default.
- W2987851504 cites W2117575563 @default.
- W2987851504 cites W2118622987 @default.
- W2987851504 cites W2130962254 @default.
- W2987851504 cites W2131570582 @default.
- W2987851504 cites W2137412908 @default.
- W2987851504 cites W2140670686 @default.
- W2987851504 cites W2140731474 @default.
- W2987851504 cites W2142344232 @default.
- W2987851504 cites W2142427836 @default.
- W2987851504 cites W2142697899 @default.