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Shiga Toxin Binds Human Platelets via Globotriaosylceramide (P k Antigen) and a Novel Platelet Glycosphingolipid
- Source :
- Infection and Immunity. 66:4355-4366
- Publication Year :
- 1998
- Publisher :
- American Society for Microbiology, 1998.
-
Abstract
- 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 high-performance 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 -β-Galα1-4galactosylglobotetraosylceramide. 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.
- Subjects :
- Blood Platelets
Glycoside Hydrolases
Shigella dysenteriae
Bacterial Toxins
Molecular Sequence Data
Immunology
Lactosylceramides
Globotriaosylceramide
Receptors, Cell Surface
Shiga Toxins
medicine.disease_cause
Microbiology
Glycosphingolipids
chemistry.chemical_compound
Shiga-like toxin
medicine
Humans
Platelet
Platelet activation
biology
Globoside
Toxin
Trihexosylceramides
Nuclear Proteins
Antigens, Nuclear
Shiga toxin
Glycosphingolipid
Phenotype
Infectious Diseases
Carbohydrate Sequence
chemistry
Molecular and Cellular Pathogenesis
biology.protein
Parasitology
Glycolipids
Subjects
Details
- ISSN :
- 10985522 and 00199567
- Volume :
- 66
- Database :
- OpenAIRE
- Journal :
- Infection and Immunity
- Accession number :
- edsair.doi.dedup.....12d77ea983ac3df6262ecb9892776c2d