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Infection and Immunity, September 1998, p. 4355-4366, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Laura L. W. Cooling,1,* Katherine E. Walker,2 Theresa Gille,3 and Theodore A. W. Koerner2,4

Department of Pathology, SUNY Health Science Center at Syracuse, Syracuse, New York,1 and Departments of Pathology2 and Pharmacology3 and DeGowin Blood Center,4 University of Iowa College of Medicine, Iowa City, Iowa

Received 18 March 1998/Returned for modification 20 April 1998/Accepted 26 June 1998

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 (Gb3) and a minor platelet glycolipid with an Rf 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 Gb3 expression. Based on glycosidase digestion and epitope mapping, band 0.03 was hypothesized to represent a novel glycosphingolipid, IV3-beta -Galalpha 1-4galactosylglobotetraosylceramide. Based on incidence, structure, and association with increased Gb3 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 Gb3 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.

* Corresponding author. Mailing address: Department of Pathology, SUNY Health Science Center at Syracuse, 750 East Adams St., Syracuse, NY 13210. Phone: (315) 464-4668. Fax: (315) 464-7130.

Infection and Immunity, September 1998, p. 4355-4366, Vol. 66, No. 9
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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