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Enterohemorrhagic Pathogenesis and the Host Response

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  • Authors: Diana Karpman1, Anne-Lie Ståhl2
  • Editors: Vanessa Sperandio3, Carolyn J. Hovde4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Pediatrics, Clinical Sciences, Lund University, Lund, Sweden; 2: Department of Pediatrics, Clinical Sciences, Lund University, Lund, Sweden; 3: University of Texas Southwestern Medical Center, Dallas, TX; 4: University of Idaho, Moscow, ID
    • Source: microbiolspec September 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.EHEC-0009-2013
  • Received 04 June 2013 Accepted 30 July 2013 Published 26 September 2014
  • Diana Karpman, [email protected]
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  • Abstract:

    Enterohemorrhagic (EHEC) is a highly pathogenic bacterial strain capable of causing watery or bloody diarrhea, the latter termed hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). HUS is defined as the simultaneous development of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The mechanism by which EHEC bacteria colonize and cause severe colitis, followed by renal failure with activated blood cells, as well as neurological symptoms, involves the interaction of bacterial virulence factors and specific pathogen-associated molecular patterns with host cells as well as the host response. The innate immune host response comprises the release of antimicrobial peptides as well as cytokines and chemokines in addition to activation and/or injury to leukocytes, platelets, and erythrocytes and activation of the complement system. Some of the bacterial interactions with the host may be protective in nature, but, when excessive, contribute to extensive tissue injury, inflammation, and thrombosis, effects that may worsen the clinical outcome of EHEC infection. This article describes aspects of the host response occurring during EHEC infection and their effects on specific organs.

  • Citation: Karpman D, Ståhl A. 2014. Enterohemorrhagic Pathogenesis and the Host Response. Microbiol Spectrum 2(5):EHEC-0009-2013. doi:10.1128/microbiolspec.EHEC-0009-2013.

References

1. Tesh VL. 2012. The induction of apoptosis by Shiga toxins and ricin. Curr Top Microbiol Immunol 357:137–178. [PubMed][CrossRef]
2. Jandhyala DM, Thorpe CM, Magun B. 2012. Ricin and Shiga toxins: effects on host cell signal transduction. Curr Top Microbiol Immunol 357:41–65. [PubMed][CrossRef]
3. Chromek M, Arvidsson I, Karpman D. 2012. The antimicrobial peptide cathelicidin protects mice from Escherichia coli O157:H7-mediated disease. PLoS One 7:e46476. [PubMed][CrossRef]
4. House B, Kus JV, Prayitno N, Mair R, Que L, Chingcuanco F, Gannon V, Cvitkovitch DG, Barnett Foster D. 2009. Acid-stress-induced changes in enterohaemorrhagic Escherichia coli O157 : H7 virulence. Microbiology 155:2907–2918. [PubMed][CrossRef]
5. Foster JW. 2004. Escherichia coli acid resistance: tales of an amateur acidophile. Nat Rev Microbiol 2:898–907. [PubMed][CrossRef]
6. Barnett Foster D. 2013. Modulation of the enterohemorrhagic E. coli virulence program through the human gastrointestinal tract. Virulence 4:315–323. [PubMed][CrossRef]
7. Phillips AD, Navabpour S, Hicks S, Dougan G, Wallis T, Frankel G. 2000. Enterohaemorrhagic Escherichia coli O157:H7 target Peyer's patches in humans and cause attaching/effacing lesions in both human and bovine intestine. Gut 47:377–381. [PubMed][CrossRef]
8. Chong Y, Fitzhenry R, Heuschkel R, Torrente F, Frankel G, Phillips AD. 2007. Human intestinal tissue tropism in Escherichia coli O157:H7—initial colonization of terminal ileum and Peyer's patches and minimal colonic adhesion ex vivo. Microbiology 153:794–802. [PubMed][CrossRef]
9. Etienne-Mesmin L, Chassaing B, Sauvanet P, Denizot J, Blanquet-Diot S, Darfeuille-Michaud A, Pradel N, Livrelli V. 2011. Interactions with M cells and macrophages as key steps in the pathogenesis of enterohemorrhagic Escherichia coli infections. PLoS One 6:e23594. [PubMed][CrossRef]
10. Miller TL, Wolin MJ. 1996. Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora. Appl Environ Microbiol 62:1589–1592. [PubMed]
11. Nakanishi N, Tashiro K, Kuhara S, Hayashi T, Sugimoto N, Tobe T. 2009. Regulation of virulence by butyrate sensing in enterohaemorrhagic Escherichia coli. Microbiology 155:521–530. [PubMed][CrossRef]
12. Herold S, Paton JC, Srimanote P, Paton AW. 2009. Differential effects of short-chain fatty acids and iron on expression of iha in Shiga-toxigenic Escherichia coli. Microbiology 155:3554–3563. [PubMed][CrossRef]
13. Jacewicz MS, Acheson DW, Mobassaleh M, Donohue-Rolfe A, Balasubramanian KA, Keusch GT. 1995. Maturational regulation of globotriaosylceramide, the Shiga-like toxin 1 receptor, in cultured human gut epithelial cells. J Clin Invest 96:1328–1335. [PubMed][CrossRef]
14. Schauber J, Svanholm C, Termen S, Iffland K, Menzel T, Scheppach W, Melcher R, Agerberth B, Luhrs H, Gudmundsson GH. 2003. Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways. Gut 52:735–741. [PubMed][CrossRef]
15. Iimura M, Gallo RL, Hase K, Miyamoto Y, Eckmann L, Kagnoff MF. 2005. Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J Immunol 174:4901–4907. [PubMed][CrossRef]
16. Islam D, Bandholtz L, Nilsson J, Wigzell H, Christensson B, Agerberth B, Gudmundsson G. 2001. Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med 7:180–185. [PubMed][CrossRef]
17. Pacheco AR, Sperandio V. 2009. Inter-kingdom signaling: chemical language between bacteria and host. Curr Opin Microbiol 12:192–198. [PubMed][CrossRef]
18. Hughes DT, Clarke MB, Yamamoto K, Rasko DA, Sperandio V. 2009. The QseC adrenergic signaling cascade in enterohemorrhagic E. coli (EHEC). PLoS Pathog 5:e1000553. [PubMed][CrossRef]
19. Malyukova I, Murray KF, Zhu C, Boedeker E, Kane A, Patterson K, Peterson JR, Donowitz M, Kovbasnjuk O. 2009. Macropinocytosis in Shiga toxin 1 uptake by human intestinal epithelial cells and transcellular transcytosis. Am J Physiol Gastrointest Liver Physiol 296:G78–G92. [PubMed][CrossRef]
20. Zumbrun SD, Hanson L, Sinclair JF, Freedy J, Melton-Celsa AR, Rodriguez-Canales J, Hanson JC, O'Brien AD. 2010. Human intestinal tissue and cultured colonic cells contain globotriaosylceramide synthase mRNA and the alternate Shiga toxin receptor globotetraosylceramide. Infect Immun 78:4488–4499. [PubMed][CrossRef]
21. Schüller S, Heuschkel R, Torrente F, Kaper JB, Phillips AD. 2007. Shiga toxin binding in normal and inflamed human intestinal mucosa. Microbes Infect 9:35–39. [PubMed][CrossRef]
22. Bell CJ, Elliott EJ, Wallace JL, Redmond DM, Payne J, Li Z, O'Loughlin EV. 2000. Do eicosanoids cause colonic dysfunction in experimental E. coli O157:H7 (EHEC) infection? Gut 46:806–812. [PubMed][CrossRef]
23. Smith WE, Kane AV, Campbell ST, Acheson DW, Cochran BH, Thorpe CM. 2003. Shiga toxin 1 triggers a ribotoxic stress response leading to p38 and JNK activation and induction of apoptosis in intestinal epithelial cells. Infect Immun 71:1497–1504. [PubMed][CrossRef]
24. Schüller S, Frankel G, Phillips AD. 2004. Interaction of Shiga toxin from Escherichia coli with human intestinal epithelial cell lines and explants: Stx2 induces epithelial damage in organ culture. Cell Microbiol 6:289–301. [PubMed][CrossRef]
25. Barnett Foster D, Abul-Milh M, Huesca M, Lingwood CA. 2000. Enterohemorrhagic Escherichia coli induces apoptosis which augments bacterial binding and phosphatidylethanolamine exposure on the plasma membrane outer leaflet. Infect Immun 68:3108–3115. [PubMed][CrossRef]
26. Kashiwamura M, Kurohane K, Tanikawa T, Deguchi A, Miyamoto D, Imai Y. 2009. Shiga toxin kills epithelial cells isolated from distal but not proximal part of mouse colon. Biol Pharm Bull 32:1614–1617. [PubMed][CrossRef]
27. Keenan KP, Sharpnack DD, Collins H, Formal SB, O'Brien AD. 1986. Morphologic evaluation of the effects of Shiga toxin and E. coli Shiga-like toxin on the rabbit intestine. Am J Pathol 125:69–80. [PubMed]
28. Békássy ZD, Calderon Toledo C, Leoj G, Kristoffersson A, Leopold SR, Perez MT, Karpman D. 2011. Intestinal damage in enterohemorrhagic Escherichia coli infection. Pediatr Nephrol 26:2059–2071. [PubMed][CrossRef]
29. Hurley BP, Jacewicz M, Thorpe CM, Lincicome LL, King AJ, Keusch GT, Acheson DW. 1999. Shiga toxins 1 and 2 translocate differently across polarized intestinal epithelial cells. Infect Immun 67:6670–6677. [PubMed]
30. Hurley BP, Thorpe CM, Acheson DW. 2001. Shiga toxin translocation across intestinal epithelial cells is enhanced by neutrophil transmigration. Infect Immun 69:6148–6155. [PubMed][CrossRef]
31. Slutsker L, Ries AA, Greene KD, Wells JG, Hutwagner L, Griffin PM. 1997. Escherichia coli O157:H7 diarrhea in the United States: clinical and epidemiologic features. Ann Intern Med 126:505–513. [PubMed][CrossRef]
32. Jung HC, Eckmann L, Yang SK, Panja A, Fierer J, Morzycka-Wroblewska E, Kagnoff MF. 1995. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest 95:55–65. [PubMed][CrossRef]
33. Thorpe CM, Hurley BP, Lincicome LL, Jacewicz MS, Keusch GT, Acheson DW. 1999. Shiga toxins stimulate secretion of interleukin-8 from intestinal epithelial cells. Infect Immun 67:5985–5993. [PubMed]
34. Thorpe CM, Smith WE, Hurley BP, Acheson DW. 2001. 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 69:6140–6147. [PubMed][CrossRef]
35. Yamasaki C, Natori Y, Zeng XT, Ohmura M, Yamasaki S, Takeda Y, Natori Y. 1999. Induction of cytokines in a human colon epithelial cell line by Shiga toxin 1 (Stx1) and Stx2 but not by non-toxic mutant Stx1 which lacks N-glycosidase activity. FEBS Lett 442:231–234. [PubMed][CrossRef]
36. Colpoys WE, Cochran BH, Carducci TM, Thorpe CM. 2005. Shiga toxins activate translational regulation pathways in intestinal epithelial cells. Cell Signal 17:891–899. [PubMed][CrossRef]
37. Tesh VL, Ramegowda B, Samuel JE. 1994. Purified Shiga-like toxins induce expression of proinflammatory cytokines from murine peritoneal macrophages. Infect Immun 62:5085–5094. [PubMed]
38. Farfan MJ, Cantero L, Vergara A, Vidal R, Torres AG. 2013. The long polar fimbriae of STEC O157:H7 induce expression of pro-inflammatory markers by intestinal epithelial cells. Vet Immunol Immunopathol 152:126–131. [PubMed][CrossRef]
39. Bellmeyer A, Cotton C, Kanteti R, Koutsouris A, Viswanathan VK, Hecht G. 2009. Enterohemorrhagic Escherichia coli suppresses inflammatory response to cytokines and its own toxin. Am J Physiol Gastrointest Liver Physiol 297:G576–G581. [PubMed][CrossRef]
40. Ho NK, Ossa JC, Silphaduang U, Johnson R, Johnson-Henry KC, Sherman PM. 2012. Enterohemorrhagic Escherichia coli O157:H7 Shiga toxins inhibit gamma interferon-mediated cellular activation. Infect Immun 80:2307–2315. [PubMed][CrossRef]
41. Karpman D, Connell H, Svensson M, Scheutz F, Alm P, Svanborg C. 1997. The role of lipopolysaccharide and Shiga-like toxin in a mouse model of Escherichia coli O157:H7 infection. J Infect Dis 175:611–620. [PubMed][CrossRef]
42. Takeda K, Akira S. 2004. TLR signaling pathways. Semin Immunol 16:3–9. [CrossRef]
43. Moresco EM, LaVine D, Beutler B. 2011. Toll-like receptors. Curr Biol 21:R488–R493. [PubMed][CrossRef]
44. Calderon Toledo C, Rogers TJ, Svensson M, Tati R, Fischer H, Svanborg C, Karpman D. 2008. Shiga toxin-mediated disease in MyD88-deficient mice infected with Escherichia coli O157:H7. Am J Pathol 173:1428–1439. [PubMed][CrossRef]
45. Torgersen ML, Engedal N, Pedersen AM, Husebye H, Espevik T, Sandvig K. 2011. Toll-like receptor 4 facilitates binding of Shiga toxin to colon carcinoma and primary umbilical vein endothelial cells. FEMS Immunol Med Microbiol 61:63–75. [PubMed][CrossRef]
46. Carbonare CB, Carbonare SB, Carneiro-Sampaio MM. 2003. Early acquisition of serum and saliva antibodies reactive to enteropathogenic Escherichia coli virulence-associated proteins by infants living in an endemic area. Pediatr Allergy Immunol 14:222–228. [PubMed][CrossRef]
47. Parissi-Crivelli A, Parissi-Crivelli JM, Giron JA. 2000. Recognition of enteropathogenic Escherichia coli virulence determinants by human colostrum and serum antibodies. J Clin Microbiol 38:2696–2700. [PubMed]
48. Karpman D, Békássy ZD, Sjögren AC, Dubois MS, Karmali MA, Mascarenhas M, Jarvis KG, Gansheroff LJ, O'Brien AD, Arbus GS, Kaper JB. 2002. Antibodies to intimin and Escherichia coli secreted proteins A and B in patients with enterohemorrhagic Escherichia coli infections. Pediatr Nephrol 17:201–211. [PubMed][CrossRef]
49. Sjögren AC, Kaper JB, Caprioli A, Karpman D. 2004. Enzyme-linked immunosorbent assay for detection of Shiga toxin-producing Escherichia coli infection by antibodies to Escherichia coli secreted protein B in children with hemolytic uremic syndrome. Eur J Clin Microbiol Infect Dis 23:208–211. [PubMed][CrossRef]
50. Noguera-Obenza M, Ochoa TJ, Gomez HF, Guerrero ML, Herrera-Insua I, Morrow AL, Ruiz-Palacios G, Pickering LK, Guzman CA, Cleary TG. 2003. Human milk secretory antibodies against attaching and effacing Escherichia coli antigens. Emerg Infect Dis 9:545–551. [CrossRef]
51. Loureiro I, Frankel G, Adu-Bobie J, Dougan G, Trabulsi LR, Carneiro-Sampaio MM. 1998. Human colostrum contains IgA antibodies reactive to enteropathogenic Escherichia coli virulence-associated proteins: intimin, BfpA, EspA, and EspB. J Pediatr Gastroenterol Nutr 27:166–171. [PubMed][CrossRef]
52. Palmeira P, Carbonare SB, Amaral JA, Tino-De-Franco M, Carneiro-Sampaio MM. 2005. Colostrum from healthy Brazilian women inhibits adhesion and contains IgA antibodies reactive with Shiga toxin-producing Escherichia coli. Eur J Pediatr 164:37–43. [PubMed][CrossRef]
53. Bitzan M, Moebius E, Ludwig K, Müller-Wiefel DE, Heesemann J, Karch H. 1991. High incidence of serum antibodies to Escherichia coli O157 lipopolysaccharide in children with hemolytic-uremic syndrome. J Pediatr 119:380–385. [PubMed][CrossRef]
54. Ludwig K, Grabhorn E, Bitzan M, Bobrowski C, Kemper MJ, Sobottka I, Laufs R, Karch H, Müller-Wiefel DE. 2002. Saliva IgM and IgA are a sensitive indicator of the humoral immune response to Escherichia coli O157 lipopolysaccharide in children with enteropathic hemolytic uremic syndrome. Pediatr Res 52:307–313. [PubMed][CrossRef]
55. Ludwig K, Bitzan M, Bobrowski C, Müller-Wiefel DE. 2002. Escherichia coli O157 fails to induce a long-lasting lipopolysaccharide-specific, measurable humoral immune response in children with hemolytic-uremic syndrome. J Infect Dis 186:566–569. [PubMed][CrossRef]
56. Palmeira P, Yu Ito L, Arslanian C, Carneiro-Sampaio MM. 2007. Passive immunity acquisition of maternal anti-enterohemorrhagic Escherichia coli (EHEC) O157:H7 IgG antibodies by the newborn. Eur J Pediatr 166:413–419. [PubMed][CrossRef]
57. Ludwig K, Karmali MA, Sarkim V, Bobrowski C, Petric M, Karch H, Muller-Wiefel DE. 2001. Antibody response to Shiga toxins Stx2 and Stx1 in children with enteropathic hemolytic-uremic syndrome. J Clin Microbiol 39:2272–2279. [PubMed][CrossRef]
58. Ludwig K, Sarkim V, Bitzan M, Karmali MA, Bobrowski C, Ruder H, Laufs R, Sobottka I, Petric M, Karch H, Muller-Wiefel DE. 2002. Shiga toxin-producing Escherichia coli infection and antibodies against Stx2 and Stx1 in household contacts of children with enteropathic hemolytic-uremic syndrome. J Clin Microbiol 40:1773–1782. [PubMed][CrossRef]
59. Martinez MB, Taddei CR, Ruiz-Tagle A, Trabulsi LR, Giron JA. 1999. Antibody response of children with enteropathogenic Escherichia coli infection to the bundle-forming pilus and locus of enterocyte effacement-encoded virulence determinants. J Infect Dis 179:269–274. [PubMed][CrossRef]
60. Calderon Toledo C, Arvidsson I, Karpman D. 2011. Cross-reactive protection against enterohemorrhagic Escherichia coli infection by enteropathogenic E. coli in a mouse model. Infect Immun 79:2224–2233. [PubMed][CrossRef]
61. Walters MD, Matthei IU, Kay R, Dillon MJ, Barratt TM. 1989. The polymorphonuclear leucocyte count in childhood haemolytic uraemic syndrome. Pediatr Nephrol 3:130–134. [PubMed][CrossRef]
62. Robson WL, Fick GH, Wilson PC. 1988. Prognostic factors in typical postdiarrhea hemolytic-uremic syndrome. Child Nephrol Urol 9:203–207. [PubMed]
63. Fernandez GC, Gomez SA, Rubel CJ, Bentancor LV, Barrionuevo P, Alduncin M, Grimoldi I, Exeni R, Isturiz MA, Palermo MS. 2005. Impaired neutrophils in children with the typical form of hemolytic uremic syndrome. Pediatr Nephrol 20:1306–1314. [PubMed][CrossRef]
64. Milford D, Taylor CM, Rafaat F, Halloran E, Dawes J. 1989. Neutrophil elastases and haemolytic uraemic syndrome. Lancet 2:1153. [PubMed][CrossRef]
65. Fitzpatrick MM, Shah V, Filler G, Dillon MJ, Barratt TM. 1992. Neutrophil activation in the haemolytic uraemic syndrome: free and complexed elastase in plasma. Pediatr Nephrol 6:50–53. [PubMed][CrossRef]
66. Hughes DA, Smith GC, Davidson JE, Murphy AV, Beattie TJ. 1996. The neutrophil oxidative burst in diarrhoea-associated haemolytic uraemic syndrome. Pediatr Nephrol 10:445–447. [PubMed][CrossRef]
67. Forsyth KD, Simpson AC, Fitzpatrick MM, Barratt TM, Levinsky RJ. 1989. Neutrophil-mediated endothelial injury in haemolytic uraemic syndrome. Lancet 2:411–414. [PubMed][CrossRef]
68. Fernandez GC, Gomez SA, Ramos MV, Bentancor LV, Fernandez-Brando RJ, Landoni VI, Lopez L, Ramirez F, Diaz M, Alduncin M, Grimoldi I, Exeni R, Isturiz MA, Palermo MS. 2007. The functional state of neutrophils correlates with the severity of renal dysfunction in children with hemolytic uremic syndrome. Pediatr Res 61:123–128. [PubMed][CrossRef]
69. Fitzpatrick MM, Shah V, Trompeter RS, Dillon MJ, Barratt TM. 1992. Interleukin-8 and polymorphoneutrophil leucocyte activation in hemolytic uremic syndrome of childhood. Kidney Int 42:951–956. [PubMed][CrossRef]
70. Liu J, He T, He Y, Zhang Z, Akahoshi T, Kondo H, Zhong S. 2002. Prolongation of functional life-span of neutrophils by recombinant verotoxin 2. Chin Med J (Engl) 115:900–903. [PubMed]
71. Ge S, Hertel B, Emden SH, Beneke J, Menne J, Haller H, von Vietinghoff S. 2012. Microparticle generation and leucocyte death in Shiga toxin-mediated HUS. Nephrol Dial Transplant 27:2768–2775. [PubMed][CrossRef]
72. Fernandez GC, Lopez MF, Gomez SA, Ramos MV, Bentancor LV, Fernandez-Brando RJ, Landoni VI, Dran GI, Meiss R, Isturiz MA, Palermo MS. 2006. Relevance of neutrophils in the murine model of haemolytic uraemic syndrome: mechanisms involved in Shiga toxin type 2-induced neutrophilia. Clin Exp Immunol 146:76–84. [PubMed][CrossRef]
73. Fukuda MN, Dell A, Oates JE, Wu P, Klock JC, 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. [PubMed]
74. Arfilli V, Carnicelli D, Rocchi L, Ricci F, Pagliaro P, Tazzari PL, Brigotti M. 2010. Shiga toxin 1 and ricin A chain bind to human polymorphonuclear leucocytes through a common receptor. Biochem J 432:173–180. [PubMed][CrossRef]
75. Geelen JM, van der Velden TJ, Te Loo DM, Boerman OC, van den Heuvel LP, Monnens LA. 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. [PubMed][CrossRef]
76. Te Loo DM, van Hinsbergh VW, van den Heuvel LP, Monnens LA. 2001. Detection of verocytotoxin bound to circulating polymorphonuclear leukocytes of patients with hemolytic uremic syndrome. J Am Soc Nephrol 12:800–806. [PubMed]
77. Tazzari PL, Ricci F, Carnicelli D, Caprioli A, Tozzi AE, 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. [PubMed][CrossRef]
78. Ståhl AL, Sartz L, Nelsson A, Békássy ZD, Karpman D. 2009. Shiga toxin and lipopolysaccharide induce platelet-leukocyte aggregates and tissue factor release, a thrombotic mechanism in hemolytic uremic syndrome. PLoS One 4:e6990. [PubMed][CrossRef]
79. Brigotti M, Tazzari PL, Ravanelli E, Carnicelli D, Rocchi L, Arfilli V, Scavia G, Minelli F, Ricci F, Pagliaro P, Ferretti AV, Pecoraro C, Paglialonga F, Edefonti A, Procaccino MA, Tozzi AE, Caprioli A. 2011. Clinical relevance of Shiga toxin concentrations in the blood of patients with hemolytic uremic syndrome. Pediatr Infect Dis J 30:486–490. [PubMed]
80. Szabady RL, Lokuta MA, Walters KB, Huttenlocher A, Welch RA. 2009. Modulation of neutrophil function by a secreted mucinase of Escherichia coli O157:H7. PLoS Pathog 5:e1000320. [PubMed][CrossRef]
81. Fernandez GC, Ramos MV, Gomez SA, Dran GI, Exeni R, Alduncin M, Grimoldi I, Vallejo G, Elias-Costa C, Isturiz MA, Palermo MS. 2005. Differential expression of function-related antigens on blood monocytes in children with hemolytic uremic syndrome. J Leukoc Biol 78:853–861. [PubMed][CrossRef]
82. Ramos MV, Fernandez GC, Patey N, Schierloh P, Exeni R, Grimoldi I, Vallejo G, Elias-Costa C, Del Carmen Sasiain M, Trachtman H, Combadiere C, Proulx F, Palermo MS. 2007. Involvement of the fractalkine pathway in the pathogenesis of childhood hemolytic uremic syndrome. Blood 109:2438–2445. [PubMed][CrossRef]
83. van Setten PA, Monnens LA, Verstraten RG, van den Heuvel LP, van Hinsbergh VW. 1996. Effects of verocytotoxin-1 on nonadherent human monocytes: binding characteristics, protein synthesis, and induction of cytokine release. Blood 88:174–183. [PubMed]
84. Guessous F, Marcinkiewicz M, Polanowska-Grabowska R, Keepers TR, Obrig T, Gear AR. 2005. Shiga toxin 2 and lipopolysaccharide cause monocytic THP-1 cells to release factors which activate platelet function. Thromb Haemost 94:1019–1027. [PubMed]
85. Murata K, Higuchi T, Takada K, Oida K, Horie S, Ishii H. 2006. Verotoxin-1 stimulation of macrophage-like THP-1 cells up-regulates tissue factor expression through activation of c-Yes tyrosine kinase: possible signal transduction in tissue factor up-regulation. Biochim Biophys Acta 1762:835–843. [PubMed][CrossRef]
86. Del Conde I, Shrimpton CN, Thiagarajan P, Lopez JA. 2005. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106:1604–1611. [PubMed][CrossRef]
87. Egorina EM, Sovershaev MA, Olsen JO, Osterud B. 2008. Granulocytes do not express but acquire monocyte-derived tissue factor in whole blood: evidence for a direct transfer. Blood 111:1208–1216. [PubMed][CrossRef]
88. Geelen JM, van der Velden TJ, van den Heuvel LP, Monnens LA. 2007. Interactions of Shiga-like toxin with human peripheral blood monocytes. Pediatr Nephrol 22:1181–1187. [PubMed][CrossRef]
89. Proulx F, Seidman EG, Karpman D. 2001. Pathogenesis of Shiga toxin-associated hemolytic uremic syndrome. Pediatr Res 50:163–171. [PubMed][CrossRef]
90. Zoja C, Buelli S, Morigi M. 2010. Shiga toxin-associated hemolytic uremic syndrome: pathophysiology of endothelial dysfunction. Pediatr Nephrol 25:2231–2240. [PubMed][CrossRef]
91. Fong JS, Kaplan BS. 1982. Impairment of platelet aggregation in hemolytic uremic syndrome: evidence for platelet “exhaustion.” Blood 60:564–570. [PubMed]
92. Sassetti B, Vizcarguenaga MI, Zanaro NL, Silva MV, Kordich L, Florentini L, Diaz M, Vitacco M, Sanchez Avalos JC. 1999. Hemolytic uremic syndrome in children: platelet aggregation and membrane glycoproteins. J Pediatr Hematol Oncol 21:123–128. [PubMed][CrossRef]
93. Galli M, Grassi A, Barbui T. 1996. Platelet-derived microvesicles in thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Thromb Haemost 75:427–431. [PubMed]
94. Walters MD, Levin M, Smith C, Nokes TJ, Hardisty RM, Dillon MJ, Barratt TM. 1988. Intravascular platelet activation in the hemolytic uremic syndrome. Kidney Int 33:107–115. [PubMed][CrossRef]
95. Keepers TR, Psotka MA, Gross LK, Obrig TG. 2006. A murine model of HUS: Shiga toxin with lipopolysaccharide mimics the renal damage and physiologic response of human disease. J Am Soc Nephrol 17:3404–3414. [PubMed][CrossRef]
96. Cooling LL, Walker KE, Gille T, Koerner TA. 1998. Shiga toxin binds human platelets via globotriaosylceramide (Pk antigen) and a novel platelet glycosphingolipid. Infect Immun 66:4355–4366. [PubMed]
97. Ghosh SA, Polanowska-Grabowska RK, Fujii J, Obrig T, Gear AR. 2004. Shiga toxin binds to activated platelets. J Thromb Haemost 2:499–506. [PubMed][CrossRef]
98. Ståhl AL, Svensson M, Morgelin M, Svanborg C, Tarr PI, Mooney JC, Watkins SL, 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. [PubMed][CrossRef]
99. Karpman D, Papadopoulou D, Nilsson K, Sjögren AC, 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. [PubMed][CrossRef]
100. Semple JW, Italiano JE, Jr., Freedman J. 2011. Platelets and the immune continuum. Nat Rev Immunol 11:264–274. [PubMed][CrossRef]
101. Moore KL, Patel KD, Bruehl RE, Li F, Johnson DA, Lichenstein HS, Cummings RD, Bainton DF, McEver RP. 1995. P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin. J Cell Biol 128:661–671. [PubMed][CrossRef]
102. Michelson AD, Barnard MR, Krueger LA, Valeri CR, Furman MI. 2001. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: studies in baboons, human coronary intervention, and human acute myocardial infarction. Circulation 104:1533–1537. [PubMed][CrossRef]
103. Gear AR, Camerini D. 2003. Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation 10:335–350. [PubMed][CrossRef]
104. Shiraki R, Inoue N, Kawasaki S, Takei A, Kadotani M, Ohnishi Y, Ejiri J, Kobayashi S, Hirata K, Kawashima S, Yokoyama M. 2004. Expression of Toll-like receptors on human platelets. Thromb Res 113:379–385. [PubMed][CrossRef]
105. Andonegui G, Kerfoot SM, McNagny K, Ebbert KV, Patel KD, Kubes P. 2005. Platelets express functional Toll-like receptor-4. Blood 106:2417–2423. [PubMed][CrossRef]
106. Aslam R, Speck ER, Kim M, Crow AR, Bang KW, Nestel FP, Ni H, Lazarus AH, Freedman J, Semple JW. 2006. Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo. Blood 107:637–641. [PubMed][CrossRef]
107. Cicala C, Santacroce C, Itoh H, Douglas GJ, Page CP. 1997. A study on rat platelet responsiveness following intravenous endotoxin administration. Life Sci 60:PL31–PL38. [PubMed]
108. Jayachandran M, Brunn GJ, Karnicki K, Miller RS, Owen WG, Miller VM. 2007. In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity: implications for thrombotic risk. J Appl Physiol 102:429–433. [PubMed][CrossRef]
109. Scott T, Owens MD. 2008. Thrombocytes respond to lipopolysaccharide through Toll-like receptor-4, and MAP kinase and NF-kappaB pathways leading to expression of interleukin-6 and cyclooxygenase-2 with production of prostaglandin E2. Mol Immunol 45:1001–1008. [PubMed][CrossRef]
110. Elzey BD, Tian J, Jensen RJ, Swanson AK, Lees JR, Lentz SR, Stein CS, Nieswandt B, Wang Y, Davidson BL, Ratliff TL. 2003. Platelet-mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments. Immunity 19:9–19. [PubMed][CrossRef]
111. Viisoreanu D, Polanowska-Grabowska R, Suttitanamongkol S, Obrig TG, Gear AR. 2000. Human platelet aggregation is not altered by Shiga toxins 1 or 2. Thromb Res 98:403–410. [CrossRef]
112. Gawaz M, Neumann FJ, Dickfeld T, Koch W, Laugwitz KL, Adelsberger H, Langenbrink K, Page S, Neumeier D, Schomig A, Brand K. 1998. Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells. Circulation 98:1164–1171. [PubMed][CrossRef]
113. Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G, Kroczek RA. 1998. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 391:591–594. [PubMed][CrossRef]
114. Hollenbaugh D, Mischel-Petty N, Edwards CP, Simon JC, Denfeld RW, Kiener PA, Aruffo A. 1995. Expression of functional CD40 by vascular endothelial cells. J Exp Med 182:33–40. [PubMed][CrossRef]
115. Caprioli A, Luzzi I, Rosmini F, Resti C, Edefonti A, Perfumo F, Farina C, Goglio A, Gianviti A, Rizzoni G. 1994. Community-wide outbreak of hemolytic-uremic syndrome associated with non-O157 verocytotoxin-producing Escherichia coli. J Infect Dis 169:208–211. [PubMed][CrossRef]
116. Proulx F, Seidman E, Mariscalco MM, Lee K, Caroll S. 1999. Increased circulating levels of lipopolysaccharide binding protein in children with Escherichia coli O157:H7 hemorrhagic colitis and hemolytic uremic syndrome. Clin Diagn Lab Immunol 6:773. [PubMed]
117. Jerala R. 2007. Structural biology of the LPS recognition. Int J Med Microbiol 297:353–363. [PubMed][CrossRef]
118. Valles PG, Melechuck S, Gonzalez A, Manucha W, Bocanegra V, Valles R. 2012. Toll-like receptor 4 expression on circulating leucocytes in hemolytic uremic syndrome. Pediatr Nephrol 27:407–415. [PubMed][CrossRef]
119. Kamitsuji H, Nonami K, Murakami T, Ishikawa N, Nakayama A, Umeki Y. 2000. Elevated tissue factor circulating levels in children with hemolytic uremic syndrome caused by verotoxin-producing E. coli. Clin Nephrol 53:319–324. [PubMed]
120. Edgington TS, Mackman N, Brand K, Ruf W. 1991. The structural biology of expression and function of tissue factor. Thromb Haemost 66:67–79. [PubMed]
121. Rao LV, Rapaport SI, Bajaj SP. 1986. Activation of human factor VII in the initiation of tissue factor-dependent coagulation. Blood 68:685–691. [PubMed]
122. Monroe DM, Hoffman M. 2006. What does it take to make the perfect clot? Arterioscler Thromb Vasc Biol 26:41–48. [PubMed][CrossRef]
123. Camera M, Frigerio M, Toschi V, Brambilla M, Rossi F, Cottell DC, Maderna P, Parolari A, Bonzi R, De Vincenti O, Tremoli E. 2003. Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs. Arterioscler Thromb Vasc Biol 23:1690–1696. [PubMed][CrossRef]
124. Schwertz H, Tolley ND, Foulks JM, Denis MM, Risenmay BW, Buerke M, Tilley RE, Rondina MT, Harris EM, Kraiss LW, Mackman N, Zimmerman GA, Weyrich AS. 2006. Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenicity of human platelets. J Exp Med 203:2433–2440. [PubMed][CrossRef]
125. Panes O, Matus V, Saez CG, Quiroga T, Pereira J, Mezzano D. 2007. Human platelets synthesize and express functional tissue factor. Blood 109:5242–5250. [PubMed][CrossRef]
126. del Conde I, Nabi F, Tonda R, Thiagarajan P, Lopez JA, Kleiman NS. 2005. Effect of P-selectin on phosphatidylserine exposure and surface-dependent thrombin generation on monocytes. Arterioscler Thromb Vasc Biol 25:1065–1070. [PubMed][CrossRef]
127. Østerud B, Olsen JO. 2013. Human platelets do not express tissue factor. Thromb Res 132:112–115. [PubMed][CrossRef]
128. Bolande RP, Kaplan BS. 1985. Experimental studies on the hemolytic-uremic syndrome. Nephron 39:228–236. [PubMed][CrossRef]
129. Appiani AC, Edefonti A, Bettinelli A, Cossu MM, Paracchini ML, Rossi E. 1982. The relationship between plasma levels of the factor VIII complex and platelet release products (beta-thromboglobulin and platelet factor 4) in children with the hemolytic-uremic syndrome. Clin Nephrol 17:195–199. [PubMed]
130. van de Kar NC, van Hinsbergh VW, Brommer EJ, Monnens LA. 1994. The fibrinolytic system in the hemolytic uremic syndrome: in vivo and in vitro studies. Pediatr Res 36:257–264. [PubMed][CrossRef]
131. Tsai HM, Chandler WL, Sarode R, Hoffman R, Jelacic S, Habeeb RL, Watkins SL, Wong CS, Williams GD, Tarr PI. 2001. von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity in Escherichia coli O157:H7-associated hemolytic uremic syndrome. Pediatr Res 49:653–659. [PubMed][CrossRef]
132. Morigi M, Galbusera M, Binda E, Imberti B, Gastoldi S, Remuzzi A, Zoja C, Remuzzi G. 2001. Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress. Blood 98:1828–1835. [PubMed][CrossRef]
133. Nolasco LH, Turner NA, Bernardo A, Tao Z, Cleary TG, Dong JF, Moake JL. 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. [PubMed][CrossRef]
134. Guessous F, Marcinkiewicz M, Polanowska-Grabowska R, Kongkhum S, Heatherly D, Obrig T, Gear AR. 2005. Shiga toxin 2 and lipopolysaccharide induce human microvascular endothelial cells to release chemokines and factors that stimulate platelet function. Infect Immun 73:8306–8316. [PubMed][CrossRef]
135. Furie B, Furie BC. 2008. Mechanisms of thrombus formation. N Engl J Med 359:938–949. [PubMed][CrossRef]
136. Nevard CH, Jurd KM, Lane DA, Philippou H, Haycock GB, Hunt BJ. 1997. Activation of coagulation and fibrinolysis in childhood diarrhoea-associated haemolytic uraemic syndrome. Thromb Haemost 78:1450–1455. [PubMed]
137. Van Geet C, Proesmans W, Arnout J, Vermylen J, Declerck PJ. 1998. Activation of both coagulation and fibrinolysis in childhood hemolytic uremic syndrome. Kidney Int 54:1324–1330. [PubMed][CrossRef]
138. Chandler WL, Jelacic S, Boster DR, Ciol MA, Williams GD, Watkins SL, Igarashi T, Tarr PI. 2002. Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome. N Engl J Med 346:23–32. [PubMed][CrossRef]
139. Bergstein JM, Riley M, Bang NU. 1992. Role of plasminogen-activator inhibitor type 1 in the pathogenesis and outcome of the hemolytic uremic syndrome. N Engl J Med 327:755–759. [PubMed][CrossRef]
140. Chaisri U, Nagata M, Kurazono H, Horie H, Tongtawe P, Hayashi H, Watanabe T, Tapchaisri P, Chongsa-nguan M, Chaicumpa W. 2001. Localization of Shiga toxins of enterohaemorrhagic Escherichia coli in kidneys of paediatric and geriatric patients with fatal haemolytic uraemic syndrome. Microb Pathog 31:59–67. [PubMed][CrossRef]
141. Uchida H, Kiyokawa N, Horie H, Fujimoto J, Takeda T. 1999. The detection of Shiga toxins in the kidney of a patient with hemolytic uremic syndrome. Pediatr Res 45:133–137. [PubMed][CrossRef]
142. Karpman D, Håkansson A, Perez MT, Isaksson C, Carlemalm E, Caprioli A, Svanborg C. 1998. Apoptosis of renal cortical cells in the hemolytic-uremic syndrome: in vivo and in vitro studies. Infect Immun 66:636–644. [PubMed]
143. Buteau C, Proulx F, Chaibou M, Raymond D, Clermont MJ, Mariscalco MM, Lebel MH, Seidman E. 2000. Leukocytosis in children with Escherichia coli O157:H7 enteritis developing the hemolytic-uremic syndrome. Pediatr Infect Dis J 19:642–647. [PubMed][CrossRef]
144. Salzman MB, Ettenger RB, Cherry JD. 1991. Leukocytosis in hemolytic-uremic syndrome. Pediatr Infect Dis J 10:470–471. [PubMed][CrossRef]
145. Coad NA, Marshall T, Rowe B, Taylor CM. 1991. Changes in the postenteropathic form of the hemolytic uremic syndrome in children. Clin Nephrol 35:10–16. [PubMed]
146. Inward CD, Howie AJ, Fitzpatrick MM, Rafaat F, Milford DV, Taylor CM. 1997. Renal histopathology in fatal cases of diarrhoea-associated haemolytic uraemic syndrome. British Association for Paediatric Nephrology. Pediatr Nephrol 11:556–559. [PubMed][CrossRef]
147. Roche JK, Keepers TR, Gross LK, Seaner RM, Obrig TG. 2007. CXCL1/KC and CXCL2/MIP-2 are critical effectors and potential targets for therapy of Escherichia coli O157:H7-associated renal inflammation. Am J Pathol 170:526–537. [PubMed][CrossRef]
148. Keepers TR, Gross LK, Obrig TG. 2007. Monocyte chemoattractant protein 1, macrophage inflammatory protein 1 alpha, and RANTES recruit macrophages to the kidney in a mouse model of hemolytic-uremic syndrome. Infect Immun 75:1229–1236. [PubMed][CrossRef]
149. Garcia A, Marini RP, Catalfamo JL, Knox KA, Schauer DB, Rogers AB, Fox JG. 2008. Intravenous Shiga toxin 2 promotes enteritis and renal injury characterized by polymorphonuclear leukocyte infiltration and thrombosis in Dutch Belted rabbits. Microbes Infect 10:650–656. [PubMed][CrossRef]
150. Zoja C, Angioletti S, Donadelli R, Zanchi C, Tomasoni S, Binda E, Imberti B, te Loo M, Monnens L, Remuzzi G, Morigi M. 2002. Shiga toxin-2 triggers endothelial leukocyte adhesion and transmigration via NF-kappaB dependent up-regulation of IL-8 and MCP-1. Kidney Int 62:846–856. [PubMed][CrossRef]
151. Zanchi C, Zoja C, Morigi M, Valsecchi F, Liu XY, Rottoli D, Locatelli M, Buelli S, Pezzotta A, Mapelli P, Geelen J, Remuzzi G, Hawiger J. 2008. Fractalkine and CX3CR1 mediate leukocyte capture by endothelium in response to Shiga toxin. J Immunol 181:1460–1469. [PubMed][CrossRef]
152. Morigi M, Micheletti G, Figliuzzi M, Imberti B, Karmali MA, Remuzzi A, Remuzzi G, Zoja C. 1995. Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions. Blood 86:4553–4558. [PubMed]
153. Brigotti M, Caprioli A, Tozzi AE, Tazzari PL, Ricci F, Conte R, Carnicelli D, Procaccino MA, Minelli F, Ferretti AV, Paglialonga F, Edefonti A, Rizzoni G. 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. [PubMed][CrossRef]
154. Karpman D, Manea M, Vaziri-Sani F, Ståhl AL, Kristoffersson AC. 2006. Platelet activation in hemolytic uremic syndrome. Semin Thromb Hemost 32:128–145. [PubMed][CrossRef]
155. Stearns-Kurosawa DJ, Oh SY, Cherla RP, Lee MS, Tesh VL, Papin J, Henderson J, Kurosawa S. 2013. Distinct renal pathology and a chemotactic phenotype after enterohemorrhagic Escherichia coli Shiga toxins in non-human primate models of hemolytic uremic syndrome. Am J Pathol 182:1227–1238. [PubMed][CrossRef]
156. Lopez EL, Devoto S, Fayad A, Canepa C, Morrow AL, Cleary TG. 1992. Association between severity of gastrointestinal prodrome and long-term prognosis in classic hemolytic-uremic syndrome. J Pediatr 120:210–215. [CrossRef]
157. van Setten PA, van Hinsbergh VW, van den Heuvel LP, Preyers F, Dijkman HB, Assmann KJ, van der Velden TJ, Monnens LA. 1998. Monocyte chemoattractant protein-1 and interleukin-8 levels in urine and serum of patents with hemolytic uremic syndrome. Pediatr Res 43:759–767. [PubMed][CrossRef]
158. Decaluwe H, Harrison LM, Mariscalco MM, Gendrel D, Bohuon C, Tesh VL, Proulx F. 2006. Procalcitonin in children with Escherichia coli O157:H7 associated hemolytic uremic syndrome. Pediatr Res 59:579–583. [PubMed][CrossRef]
159. Proulx F, Toledano B, Phan V, Clermont MJ, Mariscalco MM, Seidman EG. 2002. Circulating granulocyte colony-stimulating factor, C-X-C, and C-C chemokines in children with Escherichia coli O157:H7 associated hemolytic uremic syndrome. Pediatr Res 52:928–934. [PubMed][CrossRef]
160. Masri C, Proulx F, Toledano B, Clermont MJ, Mariscalco MM, Seidman EG, Carcillo J. 2000. Soluble Fas and soluble Fas-ligand in children with Escherichia coli O157:H7-associated hemolytic uremic syndrome. Am J Kidney Dis 36:687–694. [PubMed][CrossRef]
161. Proulx F, Turgeon JP, Litalien C, Mariscalco MM, Robitaille P, Seidman E. 1998. Inflammatory mediators in Escherichia coli O157:H7 hemorrhagic colitis and hemolytic-uremic syndrome. Pediatr Infect Dis J 17:899–904. [PubMed][CrossRef]
162. Litalien C, Proulx F, Mariscalco MM, Robitaille P, Turgeon JP, Orrbine E, Rowe PC, McLaine PN, Seidman E. 1999. Circulating inflammatory cytokine levels in hemolytic uremic syndrome. Pediatr Nephrol 13:840–845. [PubMed][CrossRef]
163. van de Kar NC, Sauerwein RW, Demacker PN, Grau GE, van Hinsbergh VW, Monnens LA. 1995. Plasma cytokine levels in hemolytic uremic syndrome. Nephron 71:309–313. [PubMed][CrossRef]
164. Karpman D, Andreasson A, Thysell H, Kaplan BS, Svanborg C. 1995. Cytokines in childhood hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Pediatr Nephrol 9:694–699. [PubMed][CrossRef]
165. Proulx F, Litalien C, Turgeon JP, Mariscalco MM, Seidman E. 2000. Circulating levels of transforming growth factor-beta1 and lymphokines among children with hemolytic uremic syndrome. Am J Kidney Dis 35:29–34. [PubMed][CrossRef]
166. Inward CD, Varagunam M, Adu D, Milford DV, Taylor CM. 1997. Cytokines in haemolytic uraemic syndrome associated with verocytotoxin-producing Escherichia coli infection. Arch Dis Child 77:145–147. [PubMed][CrossRef]
167. Inward CD, Pall AA, Adu D, Milford DV, Taylor CM. 1995. Soluble circulating cell adhesion molecules in haemolytic uraemic syndrome. Pediatr Nephrol 9:574–578. [PubMed][CrossRef]
168. Murata A, Shimazu T, Yamamoto T, Taenaka N, Nagayama K, Honda T, Sugimoto H, Monden M, Matsuura N, Okada S. 1998. Profiles of circulating inflammatory- and anti-inflammatory cytokines in patients with hemolytic uremic syndrome due to E. coli O157 infection. Cytokine 10:544–548. [PubMed][CrossRef]
169. Yamamoto T, Nagayama K, Satomura K, Honda T, Okada S. 2000. Increased serum IL-10 and endothelin levels in hemolytic uremic syndrome caused by Escherichia coli O157. Nephron 84:326–332. [PubMed][CrossRef]
170. Lopez EL, Contrini MM, Devoto S, de Rosa MF, Grana MG, Genero MH, Canepa C, Gomez HF, Cleary TG. 1995. Tumor necrosis factor concentrations in hemolytic uremic syndrome patients and children with bloody diarrhea in Argentina. Pediatr Infect Dis J 14:594–598. [PubMed][CrossRef]
171. Nevard CH, Blann AD, Jurd KM, Haycock GB, Hunt BJ. 1999. Markers of endothelial cell activation and injury in childhood haemolytic uraemic syndrome. Pediatr Nephrol 13:487–492. [PubMed][CrossRef]
172. Caletti MG, Balestracci A, Roy AH. 2010. Levels of urinary transforming growth factor beta-1 in children with D+ hemolytic uremic syndrome. Pediatr Nephrol 25:1177–1180. [PubMed][CrossRef]
173. Bhowmik D. 2001. Elevated tissue factor levels in children with hemolytic uremic syndrome. Clin Nephrol 55:262. [PubMed]
174. Petruzziello-Pellegrini TN, Yuen DA, Page AV, Patel S, Soltyk AM, Matouk CC, Wong DK, Turgeon PJ, Fish JE, Ho JJ, Steer BM, Khajoee V, Tigdi J, Lee WL, Motto DG, Advani A, Gilbert RE, Karumanchi SA, Robinson LA, Tarr PI, Liles WC, Brunton JL, Marsden PA. 2012. The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice. J Clin Invest 122:759–776. [PubMed][CrossRef]
175. Louise CB, Obrig TG. 1991. Shiga toxin-associated hemolytic-uremic syndrome: combined cytotoxic effects of Shiga toxin, interleukin-1 beta, and tumor necrosis factor alpha on human vascular endothelial cells in vitro. Infect Immun 59:4173–4179. [PubMed]
176. Keusch GT, Acheson DW, Aaldering L, Erban J, Jacewicz MS. 1996. Comparison of the effects of Shiga-like toxin 1 on cytokine- and butyrate-treated human umbilical and saphenous vein endothelial cells. J Infect Dis 173:1164–1170. [PubMed][CrossRef]
177. van Setten PA, van Hinsbergh VW, van der Velden TJ, van de Kar NC, Vermeer M, Mahan JD, Assmann KJ, van den Heuvel LP, Monnens LA. 1997. Effects of TNF alpha on verocytotoxin cytotoxicity in purified human glomerular microvascular endothelial cells. Kidney Int 51:1245–1256. [PubMed][CrossRef]
178. van de Kar NC, Monnens LA, Karmali MA, van Hinsbergh VW. 1992. Tumor necrosis factor and interleukin-1 induce expression of the verocytotoxin receptor globotriaosylceramide on human endothelial cells: implications for the pathogenesis of the hemolytic uremic syndrome. Blood 80:2755–2764. [PubMed]
179. Louise CB, Obrig TG. 1992. Shiga toxin-associated hemolytic uremic syndrome: combined cytotoxic effects of shiga toxin and lipopolysaccharide (endotoxin) on human vascular endothelial cells in vitro. Infect Immun 60:1536–1543. [PubMed]
180. Kaye SA, Louise CB, Boyd B, Lingwood CA, Obrig TG. 1993. Shiga toxin-associated hemolytic uremic syndrome: interleukin-1 beta enhancement of Shiga toxin cytotoxicity toward human vascular endothelial cells in vitro. Infect Immun 61:3886–3891. [PubMed]
181. Isogai E, Isogai H, Kimura K, Hayashi S, Kubota T, Fujii N, Takeshi K. 1998. Role of tumor necrosis factor alpha in gnotobiotic mice infected with an Escherichia coli O157:H7 strain. Infect Immun 66:197–202. [PubMed]
182. Harel Y, Silva M, Giroir B, Weinberg A, Cleary TB, Beutler B. 1993. A reporter transgene indicates renal-specific induction of tumor necrosis factor (TNF) by Shiga-like toxin. Possible involvement of TNF in hemolytic uremic syndrome. J Clin Invest 92:2110–2116. [PubMed][CrossRef]
183. Lentz EK, Cherla RP, Jaspers V, Weeks BR, Tesh VL. 2010. Role of tumor necrosis factor alpha in disease using a mouse model of Shiga toxin-mediated renal damage. Infect Immun 78:3689–3699. [PubMed][CrossRef]
184. Wolski VM, Soltyk AM, Brunton JL. 2002. Tumour necrosis factor alpha is not an essential component of verotoxin 1-induced toxicity in mice. Microb Pathog 32:263–271. [PubMed][CrossRef]
185. Hughes AK, Stricklett PK, Kohan DE. 1998. Shiga toxin-1 regulation of cytokine production by human proximal tubule cells. Kidney Int 54:1093–1106. [PubMed][CrossRef]
186. Nakamura A, Johns EJ, Imaizumi A, Yanagawa Y, Kohsaka T. 2001. Activation of beta(2)-adrenoceptor prevents shiga toxin 2-induced TNF-alpha gene transcription. J Am Soc Nephrol 12:2288–2299. [PubMed]
187. Taylor FB, Jr., Tesh VL, DeBault L, Li A, Chang AC, Kosanke SD, Pysher TJ, Siegler RL. 1999. 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 154:1285–1299. [PubMed][CrossRef]
188. Hughes AK, Stricklett PK, Kohan DE. 2001. Shiga toxin-1 regulation of cytokine production by human glomerular epithelial cells. Nephron 88:14–23. [PubMed][CrossRef]
189. Akira S, Hirano T, Taga T, Kishimoto T. 1990. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J 4:2860–2867. [PubMed]
190. Ramos MV, Auvynet C, Poupel L, Rodero M, Mejias MP, Panek CA, Vanzulli S, Combadiere C, Palermo M. 2012. Chemokine receptor CCR1 disruption limits renal damage in a murine model of hemolytic uremic syndrome. Am J Pathol 180:1040–1048. [PubMed][CrossRef]
191. Karpman D, Sartz L, Johnson S. 2010. Pathophysiology of typical hemolytic uremic syndrome. Semin Thromb Hemost 36:575–585. [PubMed][CrossRef]
192. Nestoridi E, Kushak RI, Duguerre D, Grabowski EF, Ingelfinger JR. 2005. Up-regulation of tissue factor activity on human proximal tubular epithelial cells in response to Shiga toxin. Kidney Int 67:2254–2266. [PubMed][CrossRef]
193. Nestoridi E, Tsukurov O, Kushak RI, Ingelfinger JR, Grabowski EF. 2005. Shiga toxin enhances functional tissue factor on human glomerular endothelial cells: implications for the pathophysiology of hemolytic uremic syndrome. J Thromb Haemost 3:752–762. [PubMed][CrossRef]
194. Braune SA, Wichmann D, von Heinz MC, Nierhaus A, Becker H, Meyer TN, Meyer GP, Muller-Schulz M, Fricke J, de Weerth A, Hoepker WW, Fiehler J, Magnus T, Gerloff C, Panzer U, Stahl RA, Wegscheider K, Kluge S. 2013. Clinical features of critically ill patients with Shiga toxin-induced hemolytic uremic syndrome. Crit Care Med 41:1702–1710. [PubMed][CrossRef]
195. Magnus T, Rother J, Simova O, Meier-Cillien M, Repenthin J, Moller F, Gbadamosi J, Panzer U, Wengenroth M, Hagel C, Kluge S, Stahl RK, Wegscheider K, Urban P, Eckert B, Glatzel M, Fiehler J, Gerloff C. 2012. The neurological syndrome in adults during the 2011 northern German E. coli serotype O104:H4 outbreak. Brain 135:1850–1859. [PubMed][CrossRef]
196. Obata F, Tohyama K, Bonev AD, Kolling GL, Keepers TR, Gross LK, Nelson MT, Sato S, Obrig TG. 2008. Shiga toxin 2 affects the central nervous system through receptor globotriaosylceramide localized to neurons. J Infect Dis 198:1398–1406. [PubMed][CrossRef]
197. Ergonul Z, Hughes AK, Kohan DE. 2003. Induction of apoptosis of human brain microvascular endothelial cells by shiga toxin 1. J Infect Dis 187:154–158. [PubMed][CrossRef]
198. Fujii J, Wood K, Matsuda F, Carneiro-Filho BA, Schlegel KH, Yutsudo T, Binnington-Boyd B, Lingwood CA, Obata F, Kim KS, Yoshida S, Obrig T. 2008. Shiga toxin 2 causes apoptosis in human brain microvascular endothelial cells via C/EBP homologous protein. Infect Immun 76:3679–3689. [PubMed][CrossRef]
199. Shiraishi M, Ichiyama T, Matsushige T, Iwaki T, Iyoda K, Fukuda K, Makata H, Matsubara T, Furukawa S. 2008. Soluble tumor necrosis factor receptor 1 and tissue inhibitor of metalloproteinase-1 in hemolytic uremic syndrome with encephalopathy. J Neuroimmunol 196:147–152. [PubMed][CrossRef]
200. Sheth KJ, Swick HM, Haworth N. 1986. Neurological involvement in hemolytic-uremic syndrome. Ann Neurol 19:90–93. [PubMed][CrossRef]
201. Fujii J, Kita T, Yoshida S, Takeda T, Kobayashi H, Tanaka N, Ohsato K, Mizuguchi Y. 1994. Direct evidence of neuron impairment by oral infection with verotoxin-producing Escherichia coli O157:H- in mitomycin-treated mice. Infect Immun 62:3447–3453. [PubMed]
202. Sofroniew MV, Vinters HV. 2010. Astrocytes: biology and pathology. Acta Neuropathol 119:7–35. [PubMed][CrossRef]
203. Amran MY, Fujii J, Suzuki SO, Kolling GL, Villanueva SY, Kainuma M, Kobayashi H, Kameyama H, Yoshida S. 2013. Investigation of encephalopathy caused by Shiga toxin 2c-producing Escherichia coli infection in mice. PLoS One 8:e58959. [PubMed][CrossRef]
204. Fujii J, Kinoshita Y, Matsukawa A, Villanueva SY, Yutsudo T, Yoshida S. 2009. Successful steroid pulse therapy for brain lesion caused by Shiga toxin 2 in rabbits. Microb Pathog 46:179–184. [PubMed][CrossRef]
205. Ramegowda B, Samuel JE, Tesh VL. 1999. Interaction of Shiga toxins with human brain microvascular endothelial cells: cytokines as sensitizing agents. J Infect Dis 180:1205–1213. [PubMed][CrossRef]
206. Eisenhauer PB, Chaturvedi P, Fine RE, Ritchie AJ, Pober JS, Cleary TG, Newburg DS. 2001. Tumor necrosis factor alpha increases human cerebral endothelial cell Gb3 and sensitivity to Shiga toxin. Infect Immun 69:1889–1894. [PubMed][CrossRef]
207. Stricklett PK, Hughes AK, Kohan DE. 2005. Inhibition of p38 mitogen-activated protein kinase ameliorates cytokine up-regulated shigatoxin-1 toxicity in human brain microvascular endothelial cells. J Infect Dis 191:461–471. [PubMed][CrossRef]
208. Landoni VI, de Campos-Nebel M, Schierloh P, Calatayud C, Fernandez GC, Ramos MV, Rearte B, Palermo MS, Isturiz MA. 2010. Shiga toxin 1-induced inflammatory response in lipopolysaccharide-sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha. Infect Immun 78:1193–1201. [PubMed][CrossRef]
209. Landoni VI, Schierloh P, de Campos Nebel M, Fernandez GC, Calatayud C, Lapponi MJ, Isturiz MA. 2012. Shiga toxin 1 induces on lipopolysaccharide-treated astrocytes the release of tumor necrosis factor-alpha that alter brain-like endothelium integrity. PLoS Pathog 8:e1002632. [PubMed][CrossRef]
210. Monnens L, Molenaar J, Lambert PH, Proesmans W, van Munster P. 1980. The complement system in hemolytic-uremic syndrome in childhood. Clin Nephrol 13:168–171. [PubMed]
211. Robson WL, Leung AK, Fick GH, McKenna AI. 1992. Hypocomplementemia and leukocytosis in diarrhea-associated hemolytic uremic syndrome. Nephron 62:296–299. [PubMed][CrossRef]
212. Thurman JM, Marians R, Emlen W, Wood S, Smith C, Akana H, Holers VM, Lesser M, Kline M, Hoffman C, Christen E, Trachtman H. 2009. Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol 4:1920–1924. [PubMed][CrossRef]
213. Ståhl AL, Sartz L, Karpman D. 2011. Complement activation on platelet-leukocyte complexes and microparticles in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome. Blood 117:5503–5513. [PubMed][CrossRef]
214. Polley MJ, Nachman R. 1978. The human complement system in thrombin-mediated platelet function. J Exp Med 147:1713–1726. [PubMed][CrossRef]
215. Polley MJ, Nachman RL. 1983. Human platelet activation by C3a and C3a des-arg. J Exp Med 158:603–615. [PubMed][CrossRef]
216. Orth D, Khan AB, Naim A, Grif K, Brockmeyer J, Karch H, Joannidis M, Clark SJ, Day AJ, Fidanzi S, Stoiber H, Dierich MP, Zimmerhackl LB, Wurzner R. 2009. Shiga toxin activates complement and binds factor H: evidence for an active role of complement in hemolytic uremic syndrome. J Immunol 182:6394–6400. [PubMed][CrossRef]
217. Buelli S, Abbate M, Morigi M, Moioli D, Zanchi C, Noris M, Zoja C, Pusey CD, Zipfel PF, Remuzzi G. 2009. Protein load impairs factor H binding promoting complement-dependent dysfunction of proximal tubular cells. Kidney Int 75:1050–1059. [PubMed][CrossRef]
218. Proulx F, Wagner E, Toledano B, Decaluwe H, Seidman EG, Rivard GE. 2003. Mannan-binding lectin in children with Escherichia coli O157:H7 haemmorrhagic colitis and haemolytic uraemic syndrome. Clin Exp Immunol 133:360–363. [PubMed][CrossRef]
219. Karpman D, Tati R. 2013. Complement activation in thrombotic microangiopathy. Hamostaseologie 33:96–104. [PubMed][CrossRef]
220. Ueki T, Mizuno M, Uesu T, Kiso T, Nasu J, Inaba T, Kihara Y, Matsuoka Y, Okada H, Fujita T, Tsuji T. 1996. Distribution of activated complement, C3b, and its degraded fragments, iC3b/C3dg, in the colonic mucosa of ulcerative colitis (UC). Clin Exp Immunol 104:286–292. [PubMed][CrossRef]
221. Noris M, Mescia F, Remuzzi G. 2012. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol 8:622–633. [PubMed][CrossRef]
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/content/journal/microbiolspec/10.1128/microbiolspec.EHEC-0009-2013
2014-09-26
2020-09-29

Abstract:

Enterohemorrhagic (EHEC) is a highly pathogenic bacterial strain capable of causing watery or bloody diarrhea, the latter termed hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). HUS is defined as the simultaneous development of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The mechanism by which EHEC bacteria colonize and cause severe colitis, followed by renal failure with activated blood cells, as well as neurological symptoms, involves the interaction of bacterial virulence factors and specific pathogen-associated molecular patterns with host cells as well as the host response. The innate immune host response comprises the release of antimicrobial peptides as well as cytokines and chemokines in addition to activation and/or injury to leukocytes, platelets, and erythrocytes and activation of the complement system. Some of the bacterial interactions with the host may be protective in nature, but, when excessive, contribute to extensive tissue injury, inflammation, and thrombosis, effects that may worsen the clinical outcome of EHEC infection. This article describes aspects of the host response occurring during EHEC infection and their effects on specific organs.

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