1887

Abstract

Shiga toxins (Stx1 and Stx2) are responsible for initiating haemolytic uraemic syndrome, a serious extraintestinal complication caused by enterohaemorrhagic O157 : H7 infection in humans. Shiga toxins are classical AB-type exotoxins, consisting of a globotriaosylceramide (Gb)-binding B subunit pentamer and an enzymic A subunit. It is demonstrated in this study that Stx2 binds to human neutrophils by a non-classical mechanism that is independent of Gb. In contrast, the investigation revealed that Stx2 binds to murine neutrophils by the classical Gb-dependent mechanism. Moreover, whereas the human serum amyloid P (HuSAP) component inhibited Stx2 binding to murine neutrophils, HuSAP increased Stx2 binding to human neutrophils by 84.2 % (≤0.002, Student's -test). These observations may explain why HuSAP protects mice from the lethal effects of Stx2, whereas there is no indication that HuSAP plays a similar protective role in humans infected by O157 : H7.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.47282-0
2007-11-01
2019-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jmm/56/11/1423.html?itemId=/content/journal/jmm/10.1099/jmm.0.47282-0&mimeType=html&fmt=ahah

References

  1. Armstrong, G. D., Mulvey, G. L., Marcato, P., Griener, T. P., Kahan, M. C., Tennent, G. A., Sabin, C. A., Chart, H. & Pepys, M. B. ( 2006; ). Human serum amyloid P component protects against Escherichia coli O157 : H7 Shiga toxin 2 in vivo: therapeutic implications for hemolytic-uremic syndrome. J Infect Dis 193, 1120–1124.[CrossRef]
    [Google Scholar]
  2. Beutin, L., Krause, G., Zimmermann, S., Kaulfuss, S. & Gleier, K. ( 2004; ). Characterization of Shiga toxin-producing Escherichia coli strains isolated from human patients in Germany over a 3-year period. J Clin Microbiol 42, 1099–1108.[CrossRef]
    [Google Scholar]
  3. Bitzan, M., Richardson, S., Huang, C., Boyd, B., Petric, M. & Karmali, M. A. ( 1994; ). Evidence that Verotoxins (Shiga-like toxins) from Escherichia coli bind to P blood group antigens of human erythrocytes in vitro. Infect Immun 62, 3337–3347.
    [Google Scholar]
  4. Brigotti, M., Caprioli, A., Tozzi, A. E., Tazzari, P. L., Ricci, F., Conte, R., Carnicelli, D., Procaccino, M. A., Minelli, F. & other authors ( 2006; ). Shiga toxins present in the gut and in the polymorphonuclear leukocytes circulating in the blood of children with hemolytic-uremic syndrome. J Clin Microbiol 44, 313–317.[CrossRef]
    [Google Scholar]
  5. Cherla, R. P., Lee, S. Y. & Tesh, V. L. ( 2003; ). Shiga toxins and apoptosis. FEMS Microbiol Lett 228, 159–166.[CrossRef]
    [Google Scholar]
  6. Downey, G. P., Doherty, D. E., Schwab, B., III, Elson, E. L., Henson, P. M. & Worthen, G. S. ( 1990; ). Retention of leukocytes in capillaries: role of cell size and deformability. J Appl Physiol 69, 1767–1778.
    [Google Scholar]
  7. Flagler, M. J., Strasser, J. E., Chalk, C. L. & Weiss, A. A. ( 2007; ). Comparative analysis of the abilities of Shiga toxins 1 and 2 to bind to and influence neutrophil apoptosis. Infect Immun 75, 760–765.[CrossRef]
    [Google Scholar]
  8. Fraser, M. E., Fujinaga, M., Cherney, M. M., Melton-Celsa, A. R., Twiddy, E. M., O'Brien, A. D. & James, M. N. ( 2004; ). Structure of Shiga toxin type 2 (Stx2) from Escherichia coli O157 : H7. J Biol Chem 279, 27511–27517.[CrossRef]
    [Google Scholar]
  9. Fukuda, M. N., Dell, A., Oates, J. E., Wu, P., Klock, J. C. & Fukuda, M. ( 1985; ). Structures of glycosphingolipids isolated from human granulocytes. The presence of a series of linear poly-N-acetyllactosaminylceramide and its significance in glycolipids of whole blood cells. J Biol Chem 260, 1067–1082.
    [Google Scholar]
  10. Geelen, J. M., van der Velden, T. J., Te Loo, D. M., Boerman, O. C., van den Heuvel, L. P. & Monnens, L. A. ( 2007; ). Lack of specific binding of Shiga-like toxin (Verocytotoxin) and non-specific interaction of Shiga-like toxin 2 antibody with human polymorphonuclear leucocytes. Nephrol Dial Transplant 22, 749–755.[CrossRef]
    [Google Scholar]
  11. Hawkins, P. N., Tennent, G. A., Woo, P. & Pepys, M. B. ( 1991; ). Studies in vivo and in vitro of serum amyloid P component in normals and in a patient with AA amyloidosis. Clin Exp Immunol 84, 308–316.
    [Google Scholar]
  12. Head, S. C., Karmali, M. A. & Lingwood, C. A. ( 1991; ). Preparation of VT1 and VT2 hybrid toxins from their purified dissociated subunits. Evidence for B subunit modulation of a subunit function. J Biol Chem 266, 3617–3621.
    [Google Scholar]
  13. Kaplan, B. S., Meyers, K. E. & Schulman, S. L. ( 1998; ). The pathogenesis and treatment of hemolytic uremic syndrome. J Am Soc Nephrol 9, 1126–1133.
    [Google Scholar]
  14. Karmali, M. A., Petric, M., Lim, C., Fleming, P. C. & Steele, B. T. ( 1983; ). Escherichia coli cytotoxin, haemolytic-uraemic syndrome, and haemorrhagic colitis. Lancet 2, 1299–1300.
    [Google Scholar]
  15. Kimura, T., Tani, S., Matsumoto Yi, Y. & Takeda, T. ( 2001; ). Serum amyloid P component is the Shiga toxin 2-neutralizing factor in human blood. J Biol Chem 276, 41576–41579.[CrossRef]
    [Google Scholar]
  16. Kitov, P. I., Sadowska, J. M., Mulvey, G., Armstrong, G. D., Ling, H., Pannu, N. S., Read, R. J. & Bundle, D. R. ( 2000; ). Shiga-like toxins are neutralized by tailored multivalent carbohydrate ligands. Nature 403, 669–672.[CrossRef]
    [Google Scholar]
  17. Kuligowski, M. P., Kitching, A. R. & Hickey, M. J. ( 2006; ). Leukocyte recruitment to the inflamed glomerulus: a critical role for platelet-derived P-selectin in the absence of rolling. J Immunol 176, 6991–6999.[CrossRef]
    [Google Scholar]
  18. Liu, J., Akahoshi, T., Sasahana, T., Kitasato, H., Namai, R., Sasaki, T., Inoue, M. & Kondo, H. ( 1999; ). Inhibition of neutrophil apoptosis by Verotoxin 2 derived from Escherichia coli O157 : H7. Infect Immun 67, 6203–6205.
    [Google Scholar]
  19. Macher, B. A. & Klock, J. C. ( 1980; ). Isolation and chemical characterization of neutral glycosphingolipids of human neutrophils. J Biol Chem 255, 2092–2096.
    [Google Scholar]
  20. Marcato, P., Vander Helm, K., Mulvey, G. L. & Armstrong, G. D. ( 2003; ). Serum amyloid P component binding to Shiga toxin 2 requires both A subunit and B pentamer. Infect Immun 71, 6075–6078.[CrossRef]
    [Google Scholar]
  21. Menge, C., Eisenberg, T., Stamm, I. & Baljer, G. ( 2006; ). Comparison of binding and effects of Escherichia coli Shiga toxin 1 on bovine and ovine granulocytes. Vet Immunol Immunopathol 113, 392–403.[CrossRef]
    [Google Scholar]
  22. Mulvey, G., Vanmaele, R., Mrazek, M., Cahill, M. & Armstrong, G. ( 1998; ). Affinity purification of Shiga-like toxin I and Shiga-like toxin II. J Microbiol Methods 32, 247–252.[CrossRef]
    [Google Scholar]
  23. Mulvey, G. L., Marcato, P., Kitov, P. I., Sadowska, J., Bundle, D. R. & Armstrong, G. D. ( 2003; ). Assessment in mice of the therapeutic potential of tailored, multivalent Shiga toxin carbohydrate ligands. J Infect Dis 187, 640–649.[CrossRef]
    [Google Scholar]
  24. Nataro, J. P. & Kaper, J. B. ( 1998; ). Diarrheagenic Escherichia coli. Clin Microbiol Rev 11, 142–201.
    [Google Scholar]
  25. Taguchi, T., Uchida, H., Kiyokawa, N., Mori, T., Sato, N., Horie, H., Takeda, T. & Fujimoto, J. ( 1998; ). Verotoxins induce apoptosis in human renal tubular epithelium derived cells. Kidney Int 53, 1681–1688.[CrossRef]
    [Google Scholar]
  26. Tazzari, P. L., Ricci, F., Carnicelli, D., Caprioli, A., Tozzi, A. E., Rizzoni, G., Conte, R. & Brigotti, M. ( 2004; ). Flow cytometry detection of Shiga toxins in the blood from children with hemolytic uremic syndrome. Cytometry B Clin Cytom 61, 40–44.
    [Google Scholar]
  27. te Loo, D. M., Monnens, L. A., van Der Velden, T. J., Vermeer, M. A., Preyers, F., Demacker, P. N., van Den Heuvel, L. P. & van Hinsbergh, V. W. ( 2000; ). Binding and transfer of Verocytotoxin by polymorphonuclear leukocytes in hemolytic uremic syndrome. Blood 95, 3396–3402.
    [Google Scholar]
  28. te Loo, D. M., Heuvelink, A. E., de Boer, E., Nauta, J., van der Walle, J., Schroder, C., van Hinsbergh, V. W., Chart, H., van de Kar, N. C. & van den Heuvel, L. P. ( 2001a; ). Vero cytotoxin binding to polymorphonuclear leukocytes among households with children with hemolytic uremic syndrome. J Infect Dis 184, 446–450.[CrossRef]
    [Google Scholar]
  29. te Loo, D. M., van Hinsbergh, V. W., van den Heuvel, L. P. & Monnens, L. A. ( 2001b; ). Detection of Verocytotoxin bound to circulating polymorphonuclear leukocytes of patients with hemolytic uremic syndrome. J Am Soc Nephrol 12, 800–806.
    [Google Scholar]
  30. Winter, K. R., Stoffregen, W. C. & Dean-Nystrom, E. A. ( 2004; ). Shiga toxin binding to isolated porcine tissues and peripheral blood leukocytes. Infect Immun 72, 6680–6684.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.47282-0
Loading
/content/journal/jmm/10.1099/jmm.0.47282-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error