Evaluation of the role of Shiga and Shiga-like toxins in mediating direct damage to human vascular endothelial cells.
Infection with Shiga toxin- and Shiga-like toxin-producing strains of Shigella dysenteriae and Escherichia coli, respectively, can progress to the hemolytic-uremic syndrome. It has been hypothesized that circulating Shiga toxin, Shiga-like toxins, and endotoxins may contribute to the disease by directly damaging glomerular endothelial cells. The effects of these toxins on HeLa, Vero, and human vascular endothelial cells (EC) were examined. Confluent EC were sensitive to Shiga toxin but were at least 10(6)-fold less sensitive to the toxins than were Vero cells. Shiga toxin was the predominant cytotoxic factor. Lipopolysaccharides were not cytotoxic and did not augment Shiga toxin-mediated toxicity. Lower doses of Shiga toxin caused cytotoxicity when coincubated with tumor necrosis factor. The relative resistance of EC to Shiga toxin and Shiga-like toxins may be due to reduced toxin binding, as low levels of globotriaosylceramide (Gb3), the toxin-specific receptor, were found in EC membranes.
Tesh
V L
VL
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Samuel
J E
JE
Perera
L P
LP
Sharefkin
J B
JB
O'Brien
A D
AD
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity*; D001667:Binding, Competitive; D002470:Cell Survival; D002478:Cells, Cultured; D003603:Cytotoxins / Q000633:toxicity; D004730:Endothelium, Vascular / Q000166:cytology*; D004768:Enterotoxins / Q000378:metabolism / Q000633:toxicity*; D004926:Escherichia coli; D006017:Glycolipids / Q000378:metabolism; D006162:Guanylate Cyclase; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D011956:Receptors, Cell Surface / Q000032:analysis; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide; D011994:Recombinant Proteins / Q000633:toxicity; D022641:Shiga Toxin 2; D022603:Shiga Toxins; D012760:Shigella; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity; D014709:Vero Cells / Q000187:drug effects
D001427:Bacterial Toxins; D003603:Cytotoxins; D004768:Enterotoxins; D006017:Glycolipids; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D022641:Shiga Toxin 2; D022603:Shiga Toxins; D014409:Tumor Necrosis Factor-alpha; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled