Effect of endotoxin on permeability of bovine cerebral endothelial cell layers in vitro.
The effect of lipopolysaccharide (LPS) on cultured cerebral endothelial cells was investigated to assess the changes in the trans endothelial electrical resistance (TEER) across the blood-brain barrier that may occur during inflammatory diseases of the central nervous system. Primary cultures of bovine cerebral endothelial cells were cultured to tight monolayers with a TEER of 250 to 300 omega.cm2 on polycarbonate Transwell filters. LPS induced a time- and dose-dependent decline in TEER. Transport of the hydrophilic model compounds sodium fluorescein and fluorescein dextran (MR, 4 kDa) across monolayers of bovine cerebral endothelial cells increased more than 3-fold after treatment of the cells with LPS (50 ng/ml). Treatment of the monolayers with various concentrations of LPS caused a 3-to 4-fold increase in the permeability of bovine cerebral endothelial cells for [125I]bovine serum albumin, which was also preceded by a decrease in TEER. The reduction of TEER by LPS could be inhibited completely by indomethacin (10(-6)M for 30 min), a cyclooxygenase inhibitor, but not by dexamethasone, a glucocorticoid (10(-7) M for 16 hr). In conclusion, LPS administration to blood-brain barrier endothelial cells causes a decrease in TEER which leads to enhanced transport of low and high molecular weight molecules. During this process the production of eicosanoids by the endothelial cells seem to play a key role.
de Vries
H E
HE
Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, University of Leiden, Sylvius Laboratories, The Netherlands.
Blom-Roosemalen
M C
MC
de Boer
A G
AG
van Berkel
T J
TJ
Breimer
D D
DD
Kuiper
J
J
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects; D004731:Endotoxins / Q000493:pharmacokinetics / Q000494:pharmacology*; D066298:In Vitro Techniques; D010539:Permeability / Q000187:drug effects
D004731:Endotoxins