Shiga toxins and the pathophysiology of hemolytic uremic syndrome in humans and animals

Toxins

Volumn 4, Issue 11, 2012, Pages 1261-1287

  Mayer, Chad L ^a   Leibowitz, Caitlin S ^a   Kurosawa, Shinichiro ^a   Stearns Kurosawa, Deborah J ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Animal models; Enterohemorrhagic E. coli; Hemolytic uremic syndrome; Shiga toxins

Indexed keywords

ECULIZUMAB; SHIGA TOXIN; VEROTOXIN 1; VEROTOXIN 2;

ANTIINFLAMMATORY ACTIVITY; COMPLEMENT SYSTEM; CYTOKINE PRODUCTION; DISEASE MODEL; ENTEROHEMORRHAGIC ESCHERICHIA COLI; ESCHERICHIA COLI INFECTION; EXPERIMENTAL ANIMAL; GENE MUTATION; HEMOLYTIC UREMIC SYNDROME; HUMAN; INFLAMMATION; NEPHROTOXICITY; NONHUMAN; PATHOPHYSIOLOGY; REVIEW; THROMBOTIC THROMBOCYTOPENIC PURPURA;

ANIMALS; DISEASE MODELS, ANIMAL; ENTEROHEMORRHAGIC ESCHERICHIA COLI; ESCHERICHIA COLI INFECTIONS; FOODBORNE DISEASES; HEMOLYTIC-UREMIC SYNDROME; HUMANS; PURPURA, THROMBOTIC THROMBOCYTOPENIC; SHIGA TOXIN;

ANIMALIA;

EID: 84870500590     PISSN: 20726651     EISSN: None     Source Type: Journal    
DOI: 10.3390/toxins4111261     Document Type: Review

References (134)

1. Riley, L.W.; Remis, R.S.; Helgerson, S.D.; McGee, H.B.; Wells, J.G.; Davis, B.R.; Hebert, R.J.; Olcott, E.S.; Johnson, L.M.; Hargrett, N.T.; et al. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N. Engl. J. Med. 1983, 308, 681-685.
2. Bell, B.P.; Goldoft, M.; Griffin, P.M.; Davis, M.A.; Gordon, D.C.; Tarr, P.I.; Bartleson, C.A.; Lewis, J.H.; Barrett, T.J.; Wells, J.G.; et al. A multistate outbreak of Escherichia coli O157: H7-associated bloody diarrhea and hemolytic uremic syndrome from hamburgers. The Washington experience. J. Am. Med. Assoc. 1994, 272, 1349-1353.
3. Rangel, J.M.; Sparling, P.H.; Crowe, C.; Griffin, P.M.; Swerdlow, D.L. Epidemiology of Escherichia coli O157:H7 outbreaks, United States, 1982-2002. Emerg. Infect. Dis. 2005, 11, 603-609.
4. Schmidt, H.; Geitz, C.; Tarr, P.I.; Frosch, M.; Karch, H. Non-O157:H7 pathogenic Shiga toxin-producing Escherichia coli: Phenotypic and genetic profiling of virulence traits and evidence for clonality. J. Infect. Dis. 1999, 179, 115-123.
5. Beutin, L.; Zimmermann, S.; Gleier, K. Human infections with Shiga toxin-producing Escherichia coli other than serogroup O157 in germany. Emerg. Infect. Dis. 1998, 4, 635-639.
6. Savage, P.J.; Campellone, K.G.; Leong, J.M. Interaction of enterohemorrhagic Escherichia coli (EHEC) with mammalian cells: Cell adhesion, type iii secretion, and actin pedestal formation. Curr. Protoc. Microbiol. 2007, doi:10.1002/9780471729259.mc05a01s05.
7. Farfan, M.J.; Torres, A.G. Molecular mechanisms that mediate colonization of Shiga toxin-producing Escherichia coli strains. Infect. Immun. 2012, 80, 903-913.
8. Melton-Celsa, A.; Mohawk, K.; Teel, L.; O'Brien, A. Pathogenesis of Shiga-toxin producing Escherichia coli. Curr. Top Microbiol. Immunol. 2012, 357, 67-103.
9. Malyukova, I.; Murray, K.F.; Zhu, C.; Boedeker, E.; Kane, A.; Patterson, K.; Peterson, J.R.; Donowitz, M.; Kovbasnjuk, O. Macropinocytosis in Shiga toxin 1 uptake by human intestinal epithelial cells and transcellular transcytosis. Am. J. Physiol. Gastrointest. Liver Physiol. 2009, 296, G78-G92.
10. Gould, L.H.; Demma, L.; Jones, T.F.; Hurd, S.; Vugia, D.J.; Smith, K.; Shiferaw, B.; Segler, S.; Palmer, A.; Zansky, S.; et al. Hemolytic uremic syndrome and death in persons with Escherichia coli O157:H7 infection, foodborne diseases active surveillance network sites, 2000-2006. Clin. Infect. Dis. 2009, 49, 1480-1485.
11. Fukushima, H.; Hashizume, T.; Morita, Y.; Tanaka, J.; Azuma, K.; Mizumoto, Y.; Kaneno, M.; Matsuura, M.; Konma, K.; Kitani, T. Clinical experiences in Sakai City hospital during the massive outbreak of enterohemorrhagic Escherichia coli O157 infections in Sakai City, 1996. Pediatr. Int. 1999, 41, 213-217.
12. Frank, C.; Faber, M.; Askar, M.; Bernard, H.; Fruth, A.; Gilsdorf, A.; Hohle, M.; Karch, H.; Krause, G.; Prager, R.; et al. Large and ongoing outbreak of haemolytic uraemic syndrome, Germany, May 2011. Euro. Surveill. 2011, 16, 1-3.
13. Pan, D.; Das, A.; Liu, D.; Veazey, R.S.; Pahar, B. Isolation and characterization of intestinal epithelial cells from normal and SIV-infected rhesus macaques. PLoS One 2012, 7, e30247.
14. Bielaszewska, M.; Mellmann, A.; Zhang, W.; Köck, R.; Fruth, A.; Bauwens, A.; Peters, G.; Karch, H. Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: A microbiological study. Lancet Infect. Dis. 2011, 11, 671-676.
15. Frank, C.; Werber, D.; Cramer, J.P.; Askar, M.; Faber, M.; an der Heiden, M.; Bernard, H.; Fruth, A.; Prager, R.; Spode, A.; et al. Epidemic profile of Shiga-toxin-producing Wscherichia coli O104:H4 outbreak in Germany-Preliminary report. N. Engl. J. Med. 2011, 365,1771-1780.
16. Karmali, M.A.; Petric, M.; Lim, C.; Fleming, P.C.; Steele, B.T. Escherichia coli cytotoxin, haemolytic-uraemic syndrome, and haemorrhagic colitis. Lancet 1983, 2, 1299-1300.
17. Karmali, M.A.; Petric, M.; Lim, C.; Fleming, P.C.; Arbus, G.S.; Lior, H. The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli. J. Infect. Dis. 1985, 151, 775-782.
18. Wong, C.S.; Mooney, J.C.; Brandt, J.R.; Staples, A.O.; Jelacic, S.; Boster, D.R.; Watkins, S.L.; Tarr, P.I. Risk factors for the hemolytic uremic syndrome in children infected with Escherichia coli O157:H7: A multivariable analysis. Clin. Infect. Dis. 2012, 55, 33-41.
19. Kimmitt, P.T.; Harwood, C.R.; Barer, M.R. Toxin gene expression by Shiga toxin-producing Escherichia coli: The role of antibiotics and the bacterial SOS response. Emerg. Infect. Dis. 2000, 6, 458-465.
20. Buchholz, U.; Bernard, H.; Werber, D.; Bohmer, M.M.; Remschmidt, C.; Wilking, H.; Deleré, Y.; an der Heiden, M.; Adlhoch, C.; Dreesman, J.; et al. German outbreak of Escherichia coli O104:H4 associated with sprouts. N. Engl. J. Med. 2011, 365, 1763-1770.
21. Menne, J.; Nitschke, M.; Stingele, R.; Abu-Tair, M.; Beneke, J.; Bramstedt, J.; Bremer, J.P.; Brunkhorst, R.; Busch, V.; Dengler, R.; et al. Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: Case-control study. Br. Med. J. 2012, 345, e4565.
22. Corogeanu, D.; Willmes, R.; Wolke, M.; Plum, G.; Utermohlen, O.; Kronke, M. Therapeutic concentrations of antibiotics inhibit Shiga toxin release from enterohemorrhagic E. coli O104:H4 from the 2011 German outbreak. BMC Microbiol. 2012, 12, 160.
23. Rivero, M.A.; Passucci, J.A.; Rodriguez, E.M.; Signorini, M.L.; Tarabla, H.D.; Parma, A.E. Factors associated with sporadic verotoxigenic Escherichia coli infection in children with diarrhea from the central eastern area of Argentina. Foodborne Pathog. Dis. 2011, 8, 901-906.
24. Garg, A.X.; Suri, R.S.; Barrowman, N.; Rehman, F.; Matsell, D.; Rosas-Arellano, M.P.; Salvadori, M.; Haynes, R.B.; Clark, W.F. Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: A systematic review, meta-analysis, and meta-regression. JAMA 2003, 290, 1360-1370.
25. Oakes, R.S.; Kirkham, J.K.; Nelson, R.D.; Siegler, R.L. Duration of oliguria and anuria as predictors of chronic renal-related sequelae in post-diarrheal hemolytic uremic syndrome. Pediatr. Nephrol. 2008, 23, 1303-1308.
26. Obrig, T.G.; Louise, C.B.; Lingwood, C.A.; Boyd, B.; Barley-Maloney, L.; Daniel, T.O. Endothelial heterogeneity in Shiga toxin receptors and responses. J. Biol. Chem. 1993, 268, 15484-15488.
27. Zoja, C.; Angioletti, S.; Donadelli, R.; Zanchi, C.; Tomasoni, S.; Binda, E.; Imberti, B.; te Loo, M.; Monnens, L.; Remuzzi, G.; et al. Shiga toxin-2 triggers endothelial leukocyte adhesion and transmigration via NF-κb dependent up-regulation of IL-8 and MCP-1. Kidney Int. 2002, 62, 846-856.
28. Reitsma, P.H.; Versteeg, H.H.; Middeldorp, S. Mechanistic view of risk factors for venous thromboembolism. Arterioscler. Thromb. Vasc. Biol. 2012, 32, 563-568.
29. Keepers, T.R.; Psotka, M.A.; Gross, L.K.; Obrig, T.G. A murine model of HUS: Shiga toxin with lipopolysaccharide mimics the renal damage and physiologic response of human disease. J. Am. Soc. Nephrol. 2006, 17, 3404-3414.
30. Camerer, E.; Cornelissen, I.; Kataoka, H.; Duong, D.N.; Zheng, Y.-W.; Coughlin, S.R. Roles of protease-activated receptors in a mouse model of endotoxemia. Blood 2006, 107, 3912-3921.
31. Constantinescu, A.R.; Bitzan, M.; Weiss, L.S.; Christen, E.; Kaplan, B.S.; Cnaan, A.; Trachtman, H. Non-enteropathic hemolytic uremic syndrome: Causes and short-term course. Am. J. Kidney Dis. 2004, 43, 976-982.
32. Banerjee, R.; Hersh, A.L.; Newland, J.; Beekmann, S.E.; Polgreen, P.M.; Bender, J.; Shaw, J.; Copelovitch, L.; Kaplan, B.S.; Shah, S.S.; et al. Streptococcus pneumoniae-associated hemolytic uremic syndrome among children in North America. Pediatr. Infect. Dis. J. 2011, 30, 736-739.
33. Noris, M.; Remuzzi, G. Hemolytic uremic syndrome. J. Am. Soc. Nephrol. 2005, 16, 1035-1050.
34. Obrig, T.G. Escherichia coli Shiga toxin mechanisms of action in renal disease. Toxins 2010, 2, 2769-2794.
35. Karch, H.; Tarr, P.I.; Bielaszewska, M. Enterohaemorrhagic Escherichia coli in human medicine. Int. J. Med. Microbiol. 2005, 295, 405-418.
36. Paton, J.C.; Paton, A.W. Pathogenesis and diagnosis of Shiga toxin-producing Escherichia coli infections. Clin. Microbiol. Rev. 1998, 11, 450-479.
37. O'Brien, A.O.; Lively, T.A.; Chen, M.E.; Rothman, S.W.; Formal, S.B. Escherichia coli O157:H7 strains associated with haemorrhagic colitis in the United States produce a shigella dysenteriae 1 (Shiga) like cytotoxin. Lancet 1983, 1, 702.
38. Okuda, T.; Tokuda, N.; Numata, S.; Ito, M.; Ohta, M.; Kawamura, K.; Wiels, J.; Urano, T.; Tajima, O.; Furukawa, K.; et al. Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins. J. Biol. Chem. 2006, 281, 10230-10235.
39. Saxena, S.; O'Brien, A.; Ackerman, E. Shiga toxin, Shiga-like toxin II variant, and ricin are all single-site RNA N-glycosidases of 28S RNA when microinjected into Xenopus oocytes. J. Biol. Chem. 1989, 264, 596-601.
40. Mukhopadhyay, S.; Linstedt, A.D. Manganese blocks intracellular trafficking of Shiga toxin and protects against Shiga toxicosis. Science 2012, 335, 332-335.
41. Proulx, F.; Turgeon, J.P.; Litalien, C.; Mariscalco, M.M.; Robitaille, P.; Seidman, E. Inflammatory mediators in Escherichia coli O157:H7 hemorrhagic colitis and hemolytic-uremic syndrome. Pediatr. Infect. Dis. J. 1998, 17, 899-904.
42. Stearns-Kurosawa, D.J.; Collins, V.; Freeman, S.; Tesh, V.L.; Kurosawa, S. Distinct physiologic and inflammatory responses elicited in baboons after challenge with Shiga toxin type 1 or 2 from enterohemorrhagic Escherichia coli. Infect. Immun. 2010, 78, 2497-2504.
43. Smith, W.E.; Kane, A.V.; Campbell, S.T.; Acheson, D.W.K.; Cochran, B.H.; Thorpe, C.M. Shiga toxin 1 triggers a ribotoxic stress response leading to p38 and JNK activation and induction of apoptosis in intestinal epithelial cells. Infect. Immun. 2003, 71, 1497-1504.
44. Lee, S.-Y.; Lee, M.-S.; Cherla, R.P.; Tesh, V.L. Shiga toxin 1 induces apoptosis through the endoplasmic reticulum stress response in human monocytic cells. Cell. Microbiol. 2008, 10, 770-780.
45. Karpman, D.; Håkansson, A.; Perez, M.T.; Isaksson, C.; Carlemalm, E.; Caprioli, A.; Svanborg, C. Apoptosis of renal cortical cells in the hemolytic-uremic syndrome: In vivo and in vitro studies. Infect. Immun. 1998, 66, 636-644.
46. Inward, C.D.; Howie, A.J.; Fitzpatrick, M.M.; Rafaat, F.; Milford, D.V.; Taylor, C.M. Renal histopathology in fatal cases of diarrhoea-associated haemolytic uraemic syndrome. Pediatr. Nephrol 1997, 11, 556-559.
47. Chaisri, U.; Nagata, M.; Kurazono, H.; Horie, H.; Tongtawe, P.; Hayashi, H.; Watanabe, T.; Tapchaisri, P.; Chongsa-nguan, M.; Chaicumpa, W. Localization of Shiga toxins of enterohaemorrhagic Escherichia coli in kidneys of paediatric and geriatric patients with fatal haemolytic uraemic syndrome. Microb. Pathog. 2001, 31, 59-67.
48. Taylor, F.B., Jr.; Tesh, V.L.; DeBault, L.; Li, A.; Chang, A.C.; Kosanke, S.D.; Pysher, T.J.; Siegler, R.L. Characterization of the baboon responses to Shiga-like toxin: Descriptive study of a new primate model of toxic responses to Stx-1. Am. J. Pathol. 1999, 154, 1285-1299.
49. Stearns-Kurosawa, D.J.; Oh, S.-Y.; Cherla, R.P.; Lee, M.-S.; Tesh, V.L.; Papin, J.; Henderson, J.; Kurosawa, S. Distinct renal pathology and a chemotactic phenotype after enterohemorrhagic E. coli Shiga toxins. 2012, submitted for publication.
50. Morigi, M.; Micheletti, G.; Figliuzzi, M.; Imberti, B.; Karmali, M.A.; Remuzzi, A.; Remuzzi, G.; Zoja, C. Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions. Blood 1995, 86, 4553-4558.
51. Van Setten, P.A.; Monnens, L.A.; Verstraten, R.G.; van den Heuvel, L.P.; van Hinsbergh, V.W. Effects of verocytotoxin-1 on nonadherent human monocytes: Binding characteristics, protein synthesis, and induction of cytokine release. Blood 1996, 88, 174-183.
52. Richardson, S.E.; Karmali, M.A.; Becker, L.E.; Smith, C.R. The histopathology of the hemolytic uremic syndrome associated with verocytotoxin-producing Escherichia coli infections. Hum. Pathol. 1988, 19, 1102-1108.
53. King, A.J. Acute inflammation in the pathogenesis of hemolytic-uremic syndrome. Kidney Int. 2002, 61, 1553-1564.
54. Thorpe, C.M.; Hurley, B.P.; Lincicome, L.L.; Jacewicz, M.S.; Keusch, G.T.; Acheson, D.W. Shiga toxins stimulate secretion of interleukin-8 from intestinal epithelial cells. Infect. Immun. 1999, 67, 5985-5993.
55. Tesh, V.L.; Ramegowda, B.; Samuel, J.E. Purified Shiga-like toxins induce expression of proinflammatory cytokines from murine peritoneal macrophages. Infect. Immun. 1994, 62, 5085-5094.
56. Thorpe, C.M.; Smith, W.E.; Hurley, B.P.; Acheson, D.W.K. Shiga toxins induce, superinduce, and stabilize a variety of C-X-C chemokine mRNAs in intestinal epithelial cells, resulting in increased chemokine expression. Infect. Immun. 2001, 69, 6140-6147.
57. Zoja, C.; Buelli, S.; Morigi, M. Shiga toxin-associated hemolytic uremic syndrome: Pathophysiology of endothelial dysfunction. Pediatr. Nephrol. 2010, 25, 2231-2240.
58. Fernandez, G.C.; te Loo, M.W.; van der Velden, T.J.; van der Heuvel, L.P.; Palermo, M.S.; Monnens, L.L. Decrease of thrombomodulin contributes to the procoagulant state of endothelium in hemolytic uremic syndrome. Pediatr. Nephrol. 2003, 18, 1066-1068.
59. Weiler, H. Regulation of inflammation by the protein c system. Crit. Care Med. 2010, 38, S18-S25.
60. Esmon, C.T. The interactions between inflammation and coagulation. Br. J. Haematol. 2005, 131, 417-430.
61. Lin, S.M.; Wang, Y.M.; Lin, H.C.; Lee, K.Y.; Huang, C.D.; Liu, C.Y.; Wang, C.H.; Kuo, H.P. Serum thrombomodulin level relates to the clinical course of disseminated intravascular coagulation, multiorgan dysfunction syndrome, and mortality in patients with sepsis. Crit. Care Med. 2008, 36, 683-689.
62. Kurosawa, S.; Stearns-Kurosawa, D.J.; Kinasewitz, G.T. Soluble thrombomodulin: A sign of bad times. Crit. Care Med. 2008, 36, 985-987.
63. Karpman, D.; Manea, M.; Vaziri-Sani, F.; Stahl, A.L.; Kristoffersson, A.C. Platelet activation in hemolytic uremic syndrome. Semin. Thromb. Hemost. 2006, 32, 128-145.
64. Morigi, M.; Galbusera, M.; Binda, E.; Imberti, B.; Gastoldi, S.; Remuzzi, A.; Zoja, C.; Remuzzi, G. Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress. Blood 2001, 98, 1828-1835.
65. Nolasco, L.H.; Turner, N.A.; Bernardo, A.; Tao, Z.; Cleary, T.G.; Dong, J.; Moake, J.L. Hemolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von willebrand factor multimers. Blood 2005, 106, 4199-4209.
66. Walters, M.D.; Matthei, I.U.; Kay, R.; Dillon, M.J.; Barratt, T.M. The polymorphonuclear leucocyte count in childhood haemolytic uraemic syndrome. Pediatr. Nephrol. 1989, 3, 130-134.
67. Te Loo, D.M.; Monnens, L.A.; der Velden, T.J.; Vermeer, M.A.; Preyers, F.; Demacker, P.N.; van den Heuvel, L.P.; van Hinsbergh, V.W. Binding and transfer of verocytotoxin by polymorphonuclear leukocytes in hemolytic uremic syndrome. Blood 2000, 95, 3396-3402.
68. Brigotti, M. The interactions of human neutrophils with Shiga toxins and related plant toxins: Danger or safety? Toxins 2012, 4, 157-190.
69. Tazzari, P.L.; Ricci, F.; Carnicelli, D.; Caprioli, A.; Tozzi, A.E.; Rizzoni, G.; Conte, R.; Brigotti, M. Flow cytometry detection of Shiga toxins in the blood from children with hemolytic uremic syndrome. Cytometry B Clin. Cytom. 2004, 61, 40-44.
70. Brigotti, M.; Tazzari, P.L.; Ravanelli, E.; Carnicelli, D.; Rocchi, L.; Arfilli, V.; Scavia, G.; Minelli, F.; Ricci, F.; Pagliaro, P.; et al. Clinical relevance of Shiga toxin concentrations in the blood of patients with hemolytic uremic syndrome. Pediatr. Infect. Dis. J. 2011, 30, 486-490.
71. Geelen, J.M.; van der Velden, T.J.A.M.; te Loo, D.M.W.M.; Boerman, O.C.; van den Heuvel, L.P.W.J.; Monnens, L.A.H. 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. 2007, 22, 749-755.
72. Abe, H.; Okajima, K.; Okabe, H.; Takatsuki, K.; Binder, B.R. Granulocyte proteases and hydrogen peroxide synergistically inactivate thrombomodulin of endothelial cells in vitro. J. Lab. Clin. Med. 1994, 123, 874-881.
73. Zoja, C.; Locatelli, M.; Pagani, C.; Corna, D.; Zanchi, C.; Isermann, B.; Remuzzi, G.; Conway, E.M.; Noris, M. Lack of the lectin-like domain of thrombomodulin worsens Shiga toxin-associated hemolytic uremic syndrome in mice. J. Immunol. 2012.
74. Magnus, T.; Rother, J.; Simova, O.; Meier-Cillien, M.; Repenthin, J.; Moller, F.; Gbadamosi, J.; Panzer, U.; Wengenroth, M.; Hagel, C.; et al. The neurological syndrome in adults during the 2011 northern German E. coli serotype O104:H4 outbreak. Brain 2012, 135, 1850-1859.
75. Landoni, V.I.; Schierloh, P.; de Campos Nebel, M.; Fernandez, G.C.; Calatayud, C.; Lapponi, M.J.; Isturiz, M.A. Shiga toxin 1 induces on lipopolysaccharide-treated astrocytes the release of tumor necrosis factor-alpha that alter brain-like endothelium integrity. PLoS Pathog. 2012, 8, e1002632.
76. Greinacher, A.; Friesecke, S.; Abel, P.; Dressel, A.; Stracke, S.; Fiene, M.; Ernst, F.; Selleng, K.; Weissenborn, K.; Schmidt, B.M.; et al. Treatment of severe neurological deficits with igg depletion through immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic uraemic syndrome: A prospective trial. Lancet 2011, 378, 1166-1173.
77. Huang, J.; Motto, D.G.; Bundle, D.R.; Sadler, J.E. Shiga toxin B subunits induce vWF secretion by human endothelial cells and thrombotic microangiopathy in ADAMTS13-deficient mice. Blood 2010, 116, 3653-3659.
78. Zhu, Y.; Thangamani, S.; Ho, B.; Ding, J.L. The ancient origin of the complement system. EMBO J. 2005, 24, 382-394.
79. Sarma, J.V.; Ward, P.A. The complement system. Cell Tissue Res. 2011, 343, 227-235.
80. Stahl, A.L.; Sartz, L.; Karpman, D. Complement activation on platelet-leukocyte complexes and microparticles in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome. Blood 2011, 117, 5503-5513.
81. Orth, D.; Khan, A.B.; Naim, A.; Grif, K.; Brockmeyer, J.; Karch, H.; Joannidis, M.; Clark, S.J.; Day, A.J.; Fidanzi, S.; et al. Shiga toxin activates complement and binds factor H: Evidence for an active role of complement in hemolytic uremic syndrome. J. Immunol. 2009, 182, 6394-6400.
82. Morigi, M.; Galbusera, M.; Gastoldi, S.; Locatelli, M.; Buelli, S.; Pezzotta, A.; Pagani, C.; Noris, M.; Gobbi, M.; Stravalaci, M.; et al. Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis. J. Immunol. 2011, 187, 172-180.
83. Thurman, J.M.; Marians, R.; Emlen, W.; Wood, S.; Smith, C.; Akana, H.; Holers, V.M.; Lesser, M.; Kline, M.; Hoffman, C.; et al. Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome. Clin. J. Am. Soc. Nephrol. 2009, 4, 1920-1924.
84. Lapeyraque, A.L.; Malina, M.; Fremeaux-Bacchi, V.; Boppel, T.; Kirschfink, M.; Oualha, M.; Proulx, F.; Clermont, M.J.; Le Deist, F.; Niaudet, P.; et al. Eculizumab in severe Shiga-toxin-associated HUS. N. Engl. J. Med. 2011, 364, 2561-2563.
85. Nurnberger, J.; Philipp, T.; Witzke, O.; Opazo Saez, A.; Vester, U.; Baba, H.A.; Kribben, A.; Zimmerhackl, L.B.; Janecke, A.R.; Nagel, M.; et al. Eculizumab for atypical hemolytic-uremic syndrome. N. Engl. J. Med. 2009, 360, 542-544.
86. Artunc, F. Treating Shiga toxin induced haemolytic uraemic syndrome. Br. J. Haematol. 2012, 345, e4598.
87. Ruggenenti, P.; Remuzzi, G. Thrombotic microangiopathy: E. coli O104:H4 German outbreak: A missed opportunity. Nat. Rev. Nephrol. 2012, 8, 558-560.
88. Noris, M.; Caprioli, J.; Bresin, E.; Mossali, C.; Pianetti, G.; Gamba, S.; Daina, E.; Fenili, C.; Castelletti, F.; Sorosina, A.; et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin. J. Am. Soc. Nephrol. 2010, 5, 1844-1859.
89. Kavanagh, D.; Goodship, T. Genetics and complement in atypical HUS. Pediatr. Nephrol. 2010, 25, 2431-2442.
90. Caprioli, J.; Noris, M.; Brioschi, S.; Pianetti, G.; Castelletti, F.; Bettinaglio, P.; Mele, C.; Bresin, E.; Cassis, L.; Gamba, S.; et al. Genetics of HUS: The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood 2006, 108, 1267-1279.
91. Loirat, C.; Fremeaux-Bacchi, V. Atypical hemolytic uremic syndrome. Orphanet J. Rare Dis. 2011, 6, 60.
92. Gruppo, R.A.; Rother, R.P. Eculizumab for congenital atypical hemolytic-uremic syndrome. N. Engl. J. Med. 2009, 360, 544-546.
93. Delvaeye, M.; Noris, M.; de Vriese, A.; Esmon, C.T.; Esmon, N.L.; Ferrell, G.; Del-Favero, J.; Plaisance, S.; Claes, B.; Lambrechts, D.; et al. Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N. Engl. J. Med. 2009, 361, 345-357.
94. Warwicker, P.; Goodship, T.H.; Donne, R.L.; Pirson, Y.; Nicholls, A.; Ward, R.M.; Turnpenny, P.; Goodship, J.A. Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int. 1998, 53, 836-844.
95. Richards, A.; Kathryn Liszewski, M.; Kavanagh, D.; Fang, C.J.; Moulton, E.; Fremeaux-Bacchi, V.; Remuzzi, G.; Noris, M.; Goodship, T.H.; Atkinson, J.P. Implications of the initial mutations in membrane cofactor protein (MCP; CD46) leading to atypical hemolytic uremic syndrome. Mol. Immunol. 2007, 44, 111-122.
96. Goicoechea de Jorge, E.; Harris, C.L.; Esparza-Gordillo, J.; Carreras, L.; Arranz, E.A.; Garrido, C.A.; Lopez-Trascasa, M.; Sanchez-Corral, P.; Morgan, B.P.; Rodriguez de Cordoba, S. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc. Natl. Acad. Sci. USA 2007, 104, 240-245.
97. Fremeaux-Bacchi, V.; Miller, E.C.; Liszewski, M.K.; Strain, L.; Blouin, J.; Brown, A.L.; Moghal, N.; Kaplan, B.S.; Weiss, R.A.; Lhotta, K.; et al. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood 2008, 112, 4948-4952.
98. Fang, C.J.; Fremeaux-Bacchi, V.; Liszewski, M.K.; Pianetti, G.; Noris, M.; Goodship, T.H.; Atkinson, J.P. Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (ahus), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome. Blood 2008, 111, 624-632.
99. Tsai, H.M. Pathophysiology of thrombotic thrombocytopenic purpura. Int. J. Hematol. 2010, 91, 1-19.
100. Saland, J.M.; Ruggenenti, P.; Remuzzi, G. Liver-kidney transplantation to cure atypical hemolytic uremic syndrome. J. Am. Soc. Nephrol. 2009, 20, 940-949.
101. Motto, D.G.; Chauhan, A.K.; Zhu, G.; Homeister, J.; Lamb, C.B.; Desch, K.C.; Zhang, W.; Tsai, H.M.; Wagner, D.D.; Ginsburg, D. Shiga toxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice. J. Clin. Invest. 2005, 115, 2752-2761.
102. Melton-Celsa, A.R.; O'Brien, A.D. Animal models for STEC-mediated disease. Methods Mol. Med. 2003, 73, 291-305.
103. Gunzer, F.; Hennig-Pauka, I.; Waldmann, K.-H.; Sandhoff, R.; Grone, H.-J.; Kreipe, H.-H.; Matussek, A.; Mengel, M. Gnotobiotic piglets develop thrombotic microangiopathy after oral infection with enterohemorrhagic Escherichia coli. Am. J. Clin. Pathol. 2002, 118, 364-375.
104. Myhal, M.L.; Laux, D.C.; Cohen, P.S. Relative colonizing abilities of human fecal and K 12 strains of Escherichia coli in the large intestines of streptomycin-treated mice. Eur. J. Clin. Microbiol. 1982, 1, 186-192.
105. Wadolkowski, E.A.; Burris, J.A.; O'Brien, A.D. Mouse model for colonization and disease caused by enterohemorrhagic Escherichia coli O157:H7. Infect. Immun. 1990, 58, 2438-2445.
106. Fujii, J.; Kita, T.; Yoshida, S.; Takeda, T.; Kobayashi, H.; Tanaka, N.; Ohsato, K.; Mizuguchi, Y. Direct evidence of neuron impairment by oral infection with verotoxin-producing Escherichia coli O157:H-in mitomycin-treated mice. Infect. Immun. 1994, 62, 3447-3453.
107. Isogai, E.; Isogai, H.; Kimura, K.; Hayashi, S.; Kubota, T.; Fujii, N.; Takeshi, K. Role of tumor necrosis factor alpha in gnotobiotic mice infected with an Escherichia coli O157:H7 strain. Infect. Immun. 1998, 66, 197-202.
108. Karpman, D.; Connell, H.; Svensson, M.; Scheutz, F.; Alm, P.; Svanborg, C. The role of lipopolysaccharide and Shiga-like toxin in a mouse model of Escherichia coli O157:H7 infection. J. Infect. Dis. 1997, 175, 611-620.
109. Brando, R.J.; Miliwebsky, E.; Bentancor, L.; Deza, N.; Baschkier, A.; Ramos, M.V.; Fernandez, G.C.; Meiss, R.; Rivas, M.; Palermo, M.S. Renal damage and death in weaned mice after oral infection with Shiga toxin 2-producing Escherichia coli strains. Clin. Exp. Immunol. 2008, 153, 297-306.
110. Kurioka, T.; Yunou, Y.; Kita, E. Enhancement of susceptibility to Shiga toxin-producing Escherichia coli O157:H7 by protein calorie malnutrition in mice. Infect. Immun. 1998, 66, 1726-1734.
111. Garcia, A.; Bosques, C.J.; Wishnok, J.S.; Feng, Y.; Karalius, B.J.; Butterton, J.R.; Schauer, D.B.; Rogers, A.B.; Fox, J.G. Renal injury is a consistent finding in Dutch Belted rabbits experimentally infected with enterohemorrhagic Escherichia coli. J. Infect. Dis. 2006, 193, 1125-1134.
112. Stearns-Kurosawa, D.J.; Collins, V.; Freeman, S.; Debord, D.; Nishikawa, K.; Oh, S.Y.; Leibowitz, C.S.; Kurosawa, S. Rescue from lethal Shiga toxin 2-induced renal failure with a cell-permeable peptide. Pediatr. Nephrol. 2011, 26, 2031-2039.
113. Sauter, K.A.; Melton-Celsa, A.R.; Larkin, K.; Troxell, M.L.; O'Brien, A.D.; Magun, B.E. Mouse model of hemolytic-uremic syndrome caused by endotoxin-free Shiga toxin 2 (Stx2) and protection from lethal outcome by anti-stx2 antibody. Infect. Immun. 2008, 76, 4469-4478.
114. Zotta, E.; Lago, N.; Ochoa, F.; Repetto, H.A.; Ibarra, C. Development of an experimental hemolytic uremic syndrome in rats. Pediatr. Nephrol. 2008, 23, 559-567.
115. Moon, H.W.; Whipp, S.C.; Argenzio, R.A.; Levine, M.M.; Giannella, R.A. Attaching and effacing activities of rabbit and human enteropathogenic Escherichia coli in pig and rabbit intestines. Infect. Immun. 1983, 41, 1340-1351.
116. Tzipori, S.; Wachsmuth, I.K.; Chapman, C.; Birden, R.; Brittingham, J.; Jackson, C.; Hogg, J. The pathogenesis of hemorrhagic colitis caused by Escherichia coli O157:H7 in gnotobiotic piglets. J. Infect. Dis. 1986, 154, 712-716.
117. Mohawk, K.L.; O'Brien, A.D. Mouse models of Escherichia coli O157:H7 infection and shiga toxin injection. J. Biomed. Biotechnol. 2011, 2011, 258185.
118. Al-Jumaili, I.; Burke, D.A.; Scotland, S.M.; al-Mardini, H.; Record, C.O. A method of enhancing verocytotoxin production by Escherichia coli. FEMS Microbiol. Lett. 1992, 72, 121-125.
119. MacLeod, D.L.; Gyles, C.L. Effects of culture conditions on yield of Shiga-like toxin-II from Escherichia coli. Can. J. Microbiol. 1989, 35, 623-629.
120. Lomas-Neira, J.; Perl, M.; Venet, F.; Chung, C.S.; Ayala, A. The role and source of tumor necrosis factor-alpha in hemorrhage-induced priming for septic lung injury. Shock 2012, 37, 611-620.
121. Landoni, V.I.; de Campos-Nebel, M.; Schierloh, P.; Calatayud, C.; Fernandez, G.C.; Ramos, M.V.; Rearte, B.; Palermo, M.S.; Isturiz, M.A. Shiga toxin 1-induced inflammatory response in lipopolysaccharide-sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha. Infect. Immun. 2010, 78, 1193-1201.
122. Landoni, V.I.; Schierloh, P.; de Campos Nebel, M.; Fernández, G.C.; Calatayud, C.; Lapponi, M.J.; Isturiz, M.A. Shiga toxin 1 induces on lipopolysaccharide-treated astrocytes the release of tumor necrosis factor-alpha that alter brain-like endothelium integrity. PLoS Pathog. 2012, 8, e1002632.
123. Barrett, T.J.; Potter, M.E.; Wachsmuth, I.K. Bacterial endotoxin both enhances and inhibits the toxicity of Shiga-like toxin II in rabbits and mice. Infect. Immun. 1989, 57, 3434-3437.
124. Taylor, F.B.; Toh, C.H.; Hoots, W.K.; Wada, H.; Levi, M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. On behalf of the scientific subcommittee on disseminated intravascular coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Thromb. Haemost. 2001, 86, 1327-1330.
125. Stearns-Kurosawa, D.J.; Osuchowski, M.F.; Valentine, C.; Kurosawa, S.; Remick, D.G. The pathogenesis of sepsis. Annu. Rev. Pathol. 2011, 6, 19-48.
126. Remick, D.G.; Ward, P.A. Evaluation of endotoxin models for the study of sepsis. Shock 2005, 24, 7-11.
127. Chart, H.; Smith, H.R.; Scotland, S.M.; Rowe, B.; Milford, D.V.; Taylor, C.M. Serological identification of Escherichia coli O157:H7 infection in haemolytic uraemic syndrome. Lancet 1991, 337, 138-140.
128. Bitzan, M.; Moebius, E.; Ludwig, K.; Muller-Wiefel, D.E.; Heesemann, J.; Karch, H. High incidence of serum antibodies to Escherichia coli O157 lipopolysaccharide in children with hemolytic-uremic syndrome. J. Pediatr. 1991, 119, 380-385.
129. Chart, H.; Jenkins, C. The serodiagnosis of infections caused by verocytotoxin-producing Escherichia coli. J. Appl. Microbiol. 1999, 86, 731-740.
130. Ziegler, E.J.; Fisher, C.J., Jr.; Sprung, C.L.; Straube, R.C.; Sadoff, J.C.; Foulke, G.E.; Wortel, C.H.; Fink, M.P.; Dellinger, R.P.; Teng, N.N.; et al. Treatment of gram-negative bacteremia and septic shock with HA-1a human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1a sepsis study group. N. Engl. J. Med. 1991, 324, 429-436.
131. Angus, D.C.; Birmingham, M.C.; Balk, R.A.; Scannon, P.J.; Collins, D.; Kruse, J.A.; Graham, D.R.; Dedhia, H.V.; Homann, S.; MacIntyre, N. E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: A randomized controlled trial. E5 study investigators. J. Am. Med. Asso. 2000, 283, 1723-1730.
132. Deitch, E.A. Gut-origin sepsis: Evolution of a concept. Surgeon 2012, doi:10.1016/j.surge.2012.03.003.
133. Matzinger, P. The danger model: A renewed sense of self. Science 2002, 296, 301-305.
134. Wolfson, J.J.; May, K.L.; Thorpe, C.M.; Jandhyala, D.M.; Paton, J.C.; Paton, A.W. Subtilase cytotoxin activates PERK, IRE1 and ATF6 endoplasmic reticulum stress-signalling pathways. Cell Microbiol. 2008, 10, 1775-1786.