Quantitation of the rabbit intestinal glycolipid receptor for Shiga toxin

Mobassaleh, Munir; Gross, Sonja K.; McCluer, Robert H.; Donohue‐Rolfe, Arthur; Keusch, Gerald T.

doi:10.1016/0016-5085(89)90074-7

Cited by 33 publications

(11 citation statements)

References 32 publications

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“…1). MVM from a 6-week-old rabbit, which have been reported to contain Gb3 (27), bound both VT2 and VT2e significantly (P Ͻ 0.005). MVM from a 1-week-old rabbit, which have been reported not to contain Gb3 or Gb4 (27), the receptors for VT2 and VT2e (4, 30, 35), did not bind VT2 or VT2e significantly.…”

Section: Resultsmentioning

confidence: 93%

“…MVM from a 6-week-old rabbit, which have been reported to contain Gb3 (27), bound both VT2 and VT2e significantly (P Ͻ 0.005). MVM from a 1-week-old rabbit, which have been reported not to contain Gb3 or Gb4 (27), the receptors for VT2 and VT2e (4, 30, 35), did not bind VT2 or VT2e significantly. The pattern of VT2 and VT2e binding by the small intestinal MVM from rabbits of different ages correlated with the ability of the VTs to cause fluid accumulation in ligated loops of rabbit small intestine (8,17,22).…”

Section: Resultsmentioning

confidence: 93%

“…To investigate the mechanism of intestinal absorption of VT2e from the intestine, this study examined the interaction of VT2e with the pig intestine. Comparisons were made with the rabbit small intestine because the rabbit has been used extensively as a model to study the pathogenesis of VTEC-associated intestinal and extraintestinal disease (10) and the effects of VTs in the small intestines of rabbits of different ages have been well characterized (7,11,13,15,26,27). For these reasons, the interactions of VT2e with the intestines of postweaning pigs, 1-week-old rabbits, and 6-week-old rabbits were compared.…”

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confidence: 99%

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Interaction of verotoxin 2e with pig intestine

1996

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In pigs with edema disease, verotoxin 2e (VT2e) is produced in the intestine and transported to tissues, but neither the mechanism by which toxin passes through the intestine nor its failure to induce an enterotoxic reaction is understood. Binding of VT2e to pig intestine was examined by enzyme-linked immunosorbent assay involving microvillus membranes (MVM) and crude mucus; thin-layer chromatographic overlay immunoassay with total lipids extracted from MVM; and indirect immunofluorescence of toxin bound to thin sections of jejunum, ileum, and colon. VT2e bound significantly to MVM from pig jejunum and ileum but not to crude mucus. Verotoxin 2e-binding glycolipids, globotetraosylceramide and globotriaosylceramide, were detected by thin-layer chromatographic overlay immunoassay in extracts of MVM from jejunum and ileum. Indirect immunofluorescence showed that VT2e bound to vessels within the submucosa and muscularis mucosa of the jejunum, ileum, and colon and to enterocytes at the lower portion but not at the tips of villi in the jejunum and ileum. Receptors for VT2e are therefore present in the intestine of the pig, but their role in absorption of VT2e is unclear since intraintestinal inoculation of pigs with large quantities of VT2e does not result in edema disease. Previously reported lack of enterotoxicity of verotoxins in pig intestine may be explained by the absence of toxin receptors in the villus absorptive enterocytes.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 93%

mentioning

confidence: 99%

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Interaction of verotoxin 2e with pig intestine

1996

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“…We also observed a reasonably good correlation between clinical disease and the expression of Stx receptors on other tissues. Both renal failure (11) and toxin-mediated diarrhea (49,50,55,65) could reflect Stx binding to Gb 3 and/or galabiosylceramide (Stx band 0.40) on kidney and small intestinal mucosa. On vascular endothelium, Stx binding to Gb 3 is believed to play a critical role in the pathogenesis of VTECassociated HUS and thrombotic thrombocytopenic purpura through upregulation of vascular addressins such as E-and P-selectin (68), decreased synthesis of tissue plasminogen activator and inhibitor (90), and endothelial cell death (54,62,74,91,92) with exposure of the thrombogenic subendothelium.…”

Section: Discussionmentioning

confidence: 99%

Shiga Toxin Binds Human Platelets via Globotriaosylceramide (Pk Antigen) and a Novel Platelet Glycosphingolipid

Cooling

Walker²,

Gille³

et al. 1998

Infect. Immun.

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Hemolytic-uremic syndrome is a clinical syndrome characterized by acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia that often follows infection by Shiga toxin-or verotoxin-producing strains of Escherichia coli. Because thrombocytopenia and platelet activation are hallmark features of hemolytic-uremic syndrome, we examined the ability of Shiga toxin to bind platelets by flow cytometry and highperformance thin-layer chromatography (HPTLC) of isolated platelet glycosphingolipids. By HPTLC, Shiga toxin was shown to bind globotriaosylceramide (Gb 3) and a minor platelet glycolipid with an R f of 0.03, band 0.03. In a survey of 20 human tissues, band 0.03 was identified only in platelets. In individuals, band 0.03 was expressed by 20% of donors and was specifically associated with increased platelet Gb 3 expression. Based on glycosidase digestion and epitope mapping, band 0.03 was hypothesized to represent a novel glycosphingolipid, IV 3-␤-Gal␣1-4galactosylglobotetraosylceramide. Based on incidence, structure, and association with increased Gb 3 expression, band 0.03 may represent the antithetical Luke blood group antigen. By flow cytometry, Shiga toxin bound human platelets, although the amount of Shiga toxin bound varied in donors. Differences in Shiga toxin binding to platelet membranes did not reflect differences in platelet Gb 3 expression. In contrast, there was a loose association between Shiga toxin binding and decreasing forward scatter, suggesting that Shiga toxin and verotoxins bind more efficiently to smaller, older platelets. In summary, Shiga and Shiga-like toxins may bind platelets via specific glycosphingolipid receptors. Such binding may contribute to the thrombocytopenia, platelet activation, and microthrombus formation observed in hemolytic-uremic syndrome.

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“…These effects were consistent with the observed reduction in mucosal to serosal sodium flux, without alteration in serosal to mucosal chloride flux, in toxin-treated jejunal mucosa mounted in Ussing chambers. Mobassaleh et al (23) subsequently reported that while infant rabbits were refractory to the fluid secretory effect of STX in ligated small bowel loops in the first 2 wk of life, the fluid response progressively increased after day 16 as Gb3 content increased from very low levels to adult levels by the fourth week of life (24). These data suggested that sensitivity of intestinal epithelial cells to the Shiga family of toxins is both a property of differentiated mature villus cells and, at least in the rabbit, developmentally regulated.…”

Section: Discussionmentioning

confidence: 99%