Lipopolysaccharide-mediated bovine endothelial cell injury in vitro.
Lipopolysaccharide (LPS) produced time- and dose-dependent bovine endothelial cell injury in vitro that was manifested initially by cell detachment from culture substrate with subsequent cell lysis. Bovine endothelial cell injury was observed with LPS derived from Salmonella minnesota R595, a LPS comprised only of lipid A and a trisaccharide core, as well as intact LPS preparations derived Escherichia coli and S. typhosa. LPS-mediated bovine endothelial cell detachment was prevented by incubation at 4 degrees C but was not prevented by indomethacin, lidocaine, chlorpromazine or trifluoperazine, methylprednisolone or p-bromophenacyl bromide, protease inhibitors, and catalase or superoxide dismutase. Of note, LPS-mediated injury was markedly enhanced by cycloheximide. Although augmented by serum, LPS-mediated bovine endothelial cell detachment was observed in C8-deficient serum and also in serum-free medium at higher LPS concentrations. Bovine aortic, pulmonary artery, mesenteric artery, and mesenteric vein endothelial cells were all sensitive to LPS at a concentration of 1 microgram/ml. In contrast, bovine aortic smooth muscle, human umbilical vein, goat aortic, and canine vena cava endothelial cells were unaffected by LPS at a concentration of 100 micrograms/ml. We conclude that the lipid A moiety of LPS mediates direct, complement-independent endothelial cell cytotoxicity and that this injury is not prevented by inhibitors of protein and prostaglandin synthesis, oxygen radical production, protease and phospholipase activity, and cytoskeletal function. Importantly, this direct LPS-mediated cytotoxic effect is dependent on the species from which the endothelial cells are derived.
D000818:Animals; D001808:Blood Vessels / Q000166:cytology* / Q000187:drug effects; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects*; D006041:Goats; D006801:Humans; D008050:Lipid A / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D012772:Shock, Septic / Q000503:physiopathology; D013045:Species Specificity; D013696:Temperature
D008050:Lipid A; D008070:Lipopolysaccharides