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Sphingosine‐1‐phosphate protects against brain microvascular endothelial junctional protein disorganization and barrier dysfunction caused by alcohol
Author(s) -
Alves Natascha G.,
Yuan Sarah Y.,
Breslin Jerome W.
Publication year - 2019
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12506
Subject(s) - blood–brain barrier , barrier function , tight junction , chemistry , sphingosine 1 phosphate , microbiology and biotechnology , albumin , immunofluorescence , endothelium , alcohol , vascular permeability , biochemistry , endocrinology , sphingosine , biology , immunology , central nervous system , antibody , receptor
Objective S1P has known endothelial barrier‐protective properties, but whether this extends to the BBB is unclear. We hypothesized that alcohol‐induced disruption of brain microvascular endothelial barrier function and junctional protein organization can be ameliorated by S1P treatment. Methods Cultured primary HBMEC monolayers were used to characterize endothelial‐specific mechanisms of BBB regulation. TER and apparent permeability coefficients for albumin, dextran‐4 kD a, and sodium fluorescein were used as indices of barrier function. Junctional localization of Claudin‐5, VE ‐cadherin, and β‐catenin was determined by immunofluorescence confocal microscopy. S1P was applied following treatment with alcohol. Results Alcohol significantly impaired HBMEC TER . Application of S1P after alcohol treatment resulted in a hastened recovery to the baseline HBMEC TER . Alcohol‐treated HBMEC had a significantly higher mean permeability than control that was reversed by S1P. Alcohol caused the formation of gaps between cells. Treatment with S1P (after alcohol) increased junctional localization of VE ‐Cadherin, Claudin‐5, and β‐catenin. Conclusions Alcohol impairs the barrier function and junctional organization of HBMEC monolayers. S1P enhanced barrier function and restored junctions in the presence of alcohol, and thus may be useful for restoring BBB function during alcohol intoxication.