Endotoxin enhances arachidonic acid metabolism by cultured rabbit microvascular endothelial cells
Renzi, P.M.; Flynn, J.T.
American Journal of Physiology 263(4 Pt 2): H1213-H1221
1992
ISSN/ISBN: 0002-9513 PMID: 1415770 Document Number: 403650
This study demonstrates that bacterial lipopolysaccharide and lipid A exert a significant effect on eicosanoid formation by primary cultures of microvascular endothelial cells (MECs). Qualitative studies using (14C)-arachidonic acid demonstrated that prostaglandin E-2 was the primary eicosanoid formed by MECs after 20 h of treatment with either vehicle or lipopolysaccharide. Significant, dose dependent productions of PGE-2 and prostacyclin, beginning at an endotoxin dose of 0.01 ng/ml, were quantified by radioimmunoassay in supernatants of cells treated for 20 h with lipopolysaccharide or lipid A. This eicosanoid production was inhibited by meclofenamate and cycloheximide and occurred without cellular injury. The time course and kinetics of eicosanoid production in response to endotoxin demonstrate a significant, time-related enhancement. Endotoxin-treated MECs responded to exogenous substrate with augmented PGE-2 production, suggesting enhanced prostaglandin endoperoxide synthase activity. These results demonstrate a significant interaction of endotoxin with endothelial cells of microvascular origin that results in an enhanced potential for eicosanoid metabolism. This effect may be mediated in part through induction of prostaglandin endoperoxide synthase.