title: Endothelial heterogeneity in Shiga toxin receptors and responses.
abstract: This study addresses the basis for regional microvascular susceptibility to bacterial toxins implicated in hemolytic uremic syndrome. The results indicate a relationship between the degree of Shiga toxin sensitivity of human endothelial cells from different sources and the amount of globotriaosylceramide (Gb3) glycosphingolipid receptor for Shiga toxin expressed by these cells. Cell viability and protein synthesis of renal endothelial cells were reduced to 50% by 1 pM Shiga toxin, while umbilical vein cells were not affected by > 1 nM toxin. Similarly, basal levels of Gb3 were approximately 50 times higher in renal endothelial cells than in the umbilical endothelial cells. Pre-exposure of umbilical endothelial cells to tumor necrosis factor-alpha or bacterial lipopolysaccharide increased Gb3 content 4-6-fold coincident with increases in sensitivity to cytotoxic and protein synthesis inhibitory effects of Shiga toxin. Lipopolysaccharide induction of both Gb3 and sensitivity to Shiga toxin cytotoxic action in umbilical endothelial cells was dependent on the structure of lipopolysaccharide. Neither tumor necrosis factor-alpha nor lipopolysaccharide altered the Shiga toxin sensitivity or the Gb3 content of renal endothelial cells. These data indicate that differential endothelial expression of glycolipid receptors for Shiga toxins may be responsible for localized involvement of the kidney in hemolytic uremic syndrome.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, New York 14642.
authors.forename: T G
authors.initials: TG
authors.lastname: Obrig
authors.forename: C B
authors.initials: CB
authors.lastname: Louise
authors.forename: C A
authors.initials: CA
authors.lastname: Lingwood
authors.forename: B
authors.initials: B
authors.lastname: Boyd
authors.forename: L
authors.initials: L
authors.lastname: Barley-Maloney
authors.forename: T O
authors.initials: TO
authors.lastname: Daniel
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism* / Q000633:toxicity; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006028:Glycosphingolipids / Q000096:biosynthesis; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D022603:Shiga Toxins; D012760:Shigella / Q000378:metabolism; D014281:Trihexosylceramides / Q000096:biosynthesis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014470:Umbilical Cord
chemical_list: D001427:Bacterial Toxins; D006028:Glycosphingolipids; D008070:Lipopolysaccharides; D022603:Shiga Toxins; D014281:Trihexosylceramides; D014409:Tumor Necrosis Factor-alpha; C018549:globotriaosylceramide