title: Effect of endotoxin on permeability of bovine cerebral endothelial cell layers in vitro.
abstract: 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.
authors.affiliation: Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, University of Leiden, Sylvius Laboratories, The Netherlands.
authors.forename: H E
authors.initials: HE
authors.lastname: de Vries
authors.forename: M C
authors.initials: MC
authors.lastname: Blom-Roosemalen
authors.forename: A G
authors.initials: AG
authors.lastname: de Boer
authors.forename: T J
authors.initials: TJ
authors.lastname: van Berkel
authors.forename: D D
authors.initials: DD
authors.lastname: Breimer
authors.forename: J
authors.initials: J
authors.lastname: Kuiper
mesh_terms: 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
chemical_list: D004731:Endotoxins