Structural features of endotoxin required for stimulation of endothelial cell tissue factor production; exposure of preformed tissue factor after oxidant-mediated endothelial cell injury.
Cultured human umbilical vein endothelial cells synthesize the procoagulant, tissue factor, after exposure to bacterial endotoxin. Wild-type lipopolysaccharide from Escherichia coli 0127:B8 stimulates a five- to 20-fold increase in cellular tissue factor. Similarly, rough or incomplete lipopolysaccharide subunits from mutant bacterial strains, or lipid A prepared by mild acid hydrolysis of whole endotoxin, are also stimulatory. In addition, a lipid A biosynthetic precursor, consisting of a phosphorylated glucosamine disaccharide substituted with four beta-hydroxymyristoyl residues, is stimulatory at nanomolar concentrations. Endothelial cell tissue factor is not detectable on the surface of undisrupted cells, but can activate clotting on the cell surface after oxidant-mediated cell injury. The procoagulant, tissue factor, is synthesized by endothelial cells after stimulation mediated by a moiety contained within the lipid A region of lipopolysaccharide. Exposure of clotting factors at the endothelial cell surface after cell injury suggests a mechanism for the microvascular thrombosis associated with disseminated intravascular coagulation with sepsis.
D002478:Cells, Cultured; D004211:Disseminated Intravascular Coagulation / Q000503:physiopathology*; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006801:Humans; D014471:Umbilical Veins / Q000187:drug effects* / Q000502:physiology
D004731:Endotoxins