Effect of endotoxin on permeability of bovine cerebral endothelial cell layers in vitro

Helga E. De Vries, Margret C.M. Blom-Roosemalen, Albertus G. De Boer, Theo J.C. Van Berkel, Douwe D. Breimer, Johan Kuiper

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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 Ω · 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 (M(R), 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.

Original languageEnglish
Pages (from-to)1418-1423
Number of pages6
JournalJournal of pharmacology and experimental therapeutics
Volume277
Issue number3
Publication statusPublished - Jun 1996

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