Tumor necrosis factor and interleukin-1 induce expression of the verocytotoxin receptor globotriaosylceramide on human endothelial cells: Implications for the pathogenesis of the hemolytic uremic syndrome
article
The epidemic form of the hemolytic uremic syndrome (HUS), beginning with an acute gastroenteritis, has been associated with a verocytotoxin-producing Escherichia coli infection. The endothelial cell is believed to play an important role in the pathogenesis of HUS. Endothelial cell damage by verocytotoxin-1 (VT-1) in vitro is potentiated by the additional exposure of inflammatory mediators, such as tumor necrosis factor-α (TNF-α). Preincubation of human umbilical vein endothelial cells (HUVEC) with TNF-α resulted in a 10- to 100-fold increase of specific binding sites for 125I- VT-1. Furthermore, interleukin-1 (IL-1), lymphotoxin (TNF-β), and lipopolysaccharide (LPS) also markedly increase VT-1 binding. Several hours' exposure to TNF-α was enough to enhance the number of VT-1 receptors on the endothelial cells for 2 days. The TNF-α-induced increase in VT-1 binding could be inhibited by simultaneous addition of the protein synthesis inhibitor cycloheximide. Glycolipid extracts of TNF-α-treated cells tested on thin-layer chromatography demonstrated an increase of globotriaosylceramide (GbOse3cer), a functional receptor for VT-1, which suggests that preincubation of human endothelial cells with TNF-α leads to an increase in GbOse3cer synthesis in these cells. We conclude from this study that TNF-α and IL-1 induce one (or more) enzyme(s) that is (are) rate- limiting in the synthesis of the glycolipid VT-1 receptor, GbOse3cer. These in vitro studies suggest that, in addition to VT-1, inflammatory mediators play an important role in the pathogenesis of HUS.
Chemicals/CAS: cycloheximide, 642-81-9, 66-81-9; globotriaosylceramide, 71965-57-6; thrombin, 9002-04-4; verotoxin, 108066-86-0; Bacterial Toxins; Cycloheximide, 66-81-9; globotriaosylceramide, 71965-57-6; Glycolipids; Interleukin-1; Lipopolysaccharides; Receptors, Cell Surface; Shiga-Like Toxin I; Shiga-like toxin receptor; Trihexosylceramides; Tumor Necrosis Factor
Chemicals/CAS: cycloheximide, 642-81-9, 66-81-9; globotriaosylceramide, 71965-57-6; thrombin, 9002-04-4; verotoxin, 108066-86-0; Bacterial Toxins; Cycloheximide, 66-81-9; globotriaosylceramide, 71965-57-6; Glycolipids; Interleukin-1; Lipopolysaccharides; Receptors, Cell Surface; Shiga-Like Toxin I; Shiga-like toxin receptor; Trihexosylceramides; Tumor Necrosis Factor
Topics
cell surface receptorcycloheximideglobotriaosylceramideinterleukin 6lipopolysaccharidelymphotoxinrecombinant interleukin 1recombinant interleukin 1alpharecombinant interleukin 1betarecombinant tumor necrosis factor alphathrombinverotoxinarticleconcentration responsecontrolled studycytopathogenic effectcytotoxicityendothelium cellenzyme inductionescherichia colihemolytic uremic syndromehumanhuman cellpathogenesispriority journalprotein synthesis inhibitionreceptor bindingthin layer chromatographyBacterial ToxinsCarbohydrate ConformationCarbohydrate SequenceCell SurvivalCells, CulturedCycloheximideEndothelium, VascularGlycolipidsHemolytic-Uremic SyndromeHumanInterleukin-1KineticsLipopolysaccharidesMolecular Sequence DataReceptors, Cell SurfaceShiga-Like Toxin ISupport, Non-U.S. Gov'tTime FactorsTrihexosylceramidesTumor Necrosis FactorUmbilical Veins
TNO Identifier
231743
ISSN
00064971
Source
Blood, 80(11), pp. 2755-2764.
Pages
2755-2764
Files
To receive the publication files, please send an e-mail request to TNO Repository.