Endothelial heterogeneity in Shiga toxin receptors and responses

• Published in: The Journal of biological chemistry Vol. 268; no. 21; pp. 15484 - 15488
• Main Authors: OBRIG, T. G, LOUISE, C. B, LINGWOOD, C. A, BOYD, B, BARLEY-MALONEY, L, DANIEL, T. O
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25-07-1993
• Subjects: Bacterial Toxins - metabolism; Bacterial Toxins - toxicity; Biological and medical sciences; Cell receptors; Cell structures and functions; Cells, Cultured; Endothelium, Vascular - metabolism; Fundamental and applied biological sciences. Psychology; Glycosphingolipids - biosynthesis; Hemolytic-Uremic Syndrome - etiology; Hemolytic-Uremic Syndrome - metabolism; Humans; Kidney - blood supply; Kidney - metabolism; Lipopolysaccharides - pharmacology; Miscellaneous; Molecular and cellular biology; Shiga Toxins; Shigella - metabolism; Trihexosylceramides - biosynthesis; Trihexosylceramides - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Umbilical Cord; Human; Toxin; Sphingoglycolipid; Cytotoxicity; Gene expression; Kidney; Biological receptor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)82282-7

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.