Structural features of endotoxin required for stimulation of endothelial cell tissue factor production; exposure of preformed tissue factor after oxidant-mediated endothelial cell injury

• Published in: The Journal of laboratory and clinical medicine Vol. 106; no. 1; p. 38
• Main Authors: Schorer, A E, Rick, P D, Swaim, W R, Moldow, C F
• Format: Journal Article
• Language: English
• Published: United States 01-01-1985
• Subjects: Cells, Cultured; Disseminated Intravascular Coagulation - physiopathology; Endothelium - drug effects; Endothelium - physiology; Endotoxins - pharmacology; Escherichia coli; Humans; Umbilical Veins - drug effects; Umbilical Veins - physiology
• ISSN: 0022-2143

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.