Prostanoid release of cultured liver sinusoidal endothelial cells in response to endotoxin and tumor necrosis factor

Abstract

Vascular endothelial cells release prostanoids, especially prostacyclin, when properly stimulated. In addition to short acting stimuli like thrombin and histamine an increased prostanoid release occurs in the presence of endotoxin, interleukin 1 or tumor necrosis factor (TNF). The response of sinusoidal endothelial liver cells to such stimuli - probably important in hepatic inflammatory disease - is unknown. Sinusoidal endothelial liver cells from the guinea pig were isolated by centrifugal elutriation and investigated as confluent monolayers. Their prostanoid release in response to endotoxin and human recombinant TNF was determined by radioimmunoassays and compared to that obtained with cultured human umbilical vein endothelial cells. A pronounced time- and dose-dependent release of prostanoids was found with both cell types in response to endotoxin. In contrast to umbilical vein cells, liver endothelial cells produced not only large amounts of 6-keto-PGF1 alpha and some PGE2 but also thromboxane B2. Only umbilical vein endothelial cells responded to TNF with an increased 6-keto-PGF1 alpha release, emphasising the metabolic differences between both cell types.