This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cooling, L. L. W.
Right arrow Articles by Koerner, T. A. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cooling, L. L. W.
Right arrow Articles by Koerner, T. A. W.

 Previous Article  |  Next Article 

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.


This article has been cited by other articles:

  • Stahl, A.-l., Svensson, M., Morgelin, M., Svanborg, C., Tarr, P. I., Mooney, J. C., Watkins, S. L., Johnson, R., Karpman, D. (2006). Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome. Blood 108: 167-176 [Abstract] [Full Text]  
  • Nolasco, L. H., Turner, N. A., Bernardo, A., Tao, Z., Cleary, T. G., Dong, J.-f., Moake, J. L. (2005). Hemolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers. Blood 106: 4199-4209 [Abstract] [Full Text]  
  • Yamamoto, E. T., Mizuno, M., Nishikawa, K., Miyazawa, S., Zhang, L., Matsuo, S., Natori, Y. (2005). Shiga Toxin 1 Causes Direct Renal Injury in Rats. Infect. Immun. 73: 7099-7106 [Abstract] [Full Text]  
  • Cooling, L. L. W., Kelly, K., Barton, J., Hwang, D., Koerner, T. A. W., Olson, J. D. (2005). Determinants of ABH expression on human blood platelets. Blood 105: 3356-3364 [Abstract] [Full Text]  
  • Noris, M., Remuzzi, G. (2005). Hemolytic Uremic Syndrome. J. Am. Soc. Nephrol. 16: 1035-1050 [Full Text]  
  • Zhang, X., Kiechle, F. L. (2004). Glycosphingolipids in Health and Disease. Annals of Clinical & Laboratory Science 34: 3-13 [Abstract] [Full Text]  
  • Matise, I., Cornick, N. A., Samuel, J. E., Moon, H. W. (2003). Binding of Shiga Toxin 2e to Porcine Erythrocytes In Vivo and In Vitro. Infect. Immun. 71: 5194-5201 [Abstract] [Full Text]  
  • Cooling, L. L. W., Zhang, D. S., Naides, S. J., Koerner, T. A. W. (2003). Glycosphingolipid expression in acute nonlymphocytic leukemia: common expression of shiga toxin and parvovirus B19 receptors on early myeloblasts. Blood 101: 711-721 [Abstract] [Full Text]  
  • Furukawa, K., Yokoyama, K., Sato, T., Wiels, J., Hirayama, Y., Ohta, M., Furukawa, K. (2002). Expression of the Gb3/CD77 Synthase Gene in Megakaryoblastic Leukemia Cells. IMPLICATION IN THE SENSITIVITY TO VEROTOXINS. J. Biol. Chem. 277: 11247-11254 [Abstract] [Full Text]  
  • Karpman, D., Papadopoulou, D., Nilsson, K., Sjogren, A.-C., Mikaelsson, C., Lethagen, S. (2001). Platelet activation by Shiga toxin and circulatory factors as a pathogenetic mechanism in the hemolytic uremic syndrome. Blood 97: 3100-3108 [Abstract] [Full Text]  
  • te Loo, D. M. W. M., Monnens, L. A. H., van der Velden, T. J. A. M., Vermeer, M. A., Preyers, F., Demacker, P. N. M., van den Heuvel, L. P. W. J., van Hinsbergh, V. W. M. (2000). Binding and transfer of verocytotoxin by polymorphonuclear leukocytes in hemolytic uremic syndrome. Blood 95: 3396-3402 [Abstract] [Full Text]  
  • Keusch, J. J., Manzella, S. M., Nyame, K. A., Cummings, R. D., Baenziger, J. U. (2000). Cloning of Gb3 Synthase, the Key Enzyme in Globo-series Glycosphingolipid Synthesis, Predicts a Family of alpha 1,4-Glycosyltransferases Conserved in Plants, Insects, and Mammals. J. Biol. Chem. 275: 25315-25321 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»