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

被引:0
|
作者
DeVries, HE [1 ]
BlomRoosemalen, MCM [1 ]
DeBoer, AG [1 ]
VanBerkel, TJC [1 ]
Breimer, DD [1 ]
Kuiper, J [1 ]
机构
[1] LEIDEN UNIV, LEIDEN AMSTERDAM CTR DRUG RES, DIV BIOPHARMACEUT, SYLVIUS LABS, 2300 RA LEIDEN, NETHERLANDS
来源
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS | 1996年 / 277卷 / 03期
关键词
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中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 . cm(2) 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 5-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 [I-125]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.
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页码:1418 / 1423
页数:6
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