Roles of Shiga Toxin in Pathogenesis of Hemolytic Uremic Syndrome
Abstract
Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, glomerular thrombotic microangiopathy and acute renal failure. It is most common caused by infection with Shiga toxin producing bacteria such as Shigella spp. and especially Shiga toxin-producing Escherichia coli or enterohemorrhagic Escherichia coli (EHEC). Shiga toxin (Stx) is the most important virulent factor of EHEC. After ingestion contaminated foods, Stx initially causes gastrointestinal infection and approximately 10% of cases progress to HUS, especially in children and elderly. Study of HUS pathogenesis is interesting and important for a better understanding of the pathogenesis. In this review, characterization of Stx, role of Stx and mechanisms of Stx leading to HUS were described. Furthermore, the pathogenesis associated with the complement system was elucidated. Keywords : Shiga toxin, Typical Hemolytic Uremic Syndrome, Enterohemorrhagic E. Coli (EHEC), Shiga toxin-producing E. coli (STEC), The complement systemReferences
Arvidsson, I., Stahl, A.L., Hedstrom, M.M., Kristoffersson, A.C., Rylander, C., Westman, J.S., Storry, J.R., Olsson, M.L. & Karpman, D. (2015). Shiga toxin-induced complement-mediated hemolysis and release of complement-coated red blood cell-derived microvesicles in hemolytic uremic syndrome. J Immunol, 194, 2309-2318.
Beutin, L. & Martin, A. (2012). Outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in Germany causes a paradigm shift with regard to human pathogenicity of STEC strains. J Food Prot, 75, 408-418.
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. Infection and immunity, 62, 3337-3347.
Brigotti, M., Alfieri, R., Sestili, P., Bonelli, M., Petronini, P.G., Guidarelli, A., Barbieri, L., Stirpe, F. & Sperti, S. (2002). Damage to nuclear DNA induced by Shiga toxin 1 and ricin in human endothelial cells. FASEB J, 16, 365-372.
Brigotti, M., Carnicelli, D., Arfilli, V., et al. (2013). Identification of TLR4 as the receptor that recognizes Shiga toxins in human neutrophils. J Immunol, 191, 4748-4758.
Caillaud, C., Zaloszyc, A., Licht, C., Pichault, V., Fremeaux-Bacchi, V. & Fischbach, M. (2016). CFH gene mutation in a case of Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS). Pediatr Nephrol, 31, 157-161.
Caprioli, A., Morabito, S., Brugere, H. & Oswald, E. (2005). Enterohaemorrhagic Escherichia coli: emerging issues on virulence and modes of transmission. Vet Res, 36, 289-311.
Cohen, A., Madrid-Marina, V., Estrov, Z., Freedman, M.H., Lingwood, C.A. & Dosch, H.M. (1990). Expression of glycolipid receptors to Shiga-like toxin on human B lymphocytes: a mechanism for the failure of long-lived antibody response to dysenteric disease. Int Immunol, 2, 1-8.
De Petris, L., Patrick, J., Christen, E. & Trachtman, H. (2006). Urinary podocyte mRNA excretion in children with D+HUS: a potential marker of long-term outcome. Ren Fail, 28, 475-482.
Dragon-Durey, M.A., Blanc, C., Marliot, F., Loirat, C., Blouin, J., Sautes-Fridman, C., Fridman, W.H. & Fremeaux-Bacchi, V. (2009). The high frequency of complement factor H related CFHR1 gene deletion is restricted to specific subgroups of patients with atypical haemolytic uraemic syndrome. Journal of medical genetics, 46, 447-450.
Ehrlenbach, S., Rosales, A., Posch, W., Wilflingseder, D., Hermann, M., Brockmeyer, J., Karch, H., Satchell, S.C., Wurzner, R. & Orth-Holler, D. (2013). Shiga toxin 2 reduces complement inhibitor CD59 expression on human renal tubular epithelial and glomerular endothelial cells. Infect Immun, 81, 2678-2685.
Ergonul, Z., Hughes, A.K. & Kohan, D.E. (2003). Induction of apoptosis of human brain microvascular endothelial cells by shiga toxin 1. J Infect Dis, 187, 154-158.
Fang, C.J., Fremeaux-Bacchi, V., Liszewski, M.K., Pianetti, G., Noris, M., Goodship, T.H. & Atkinson, J.P. (2008). Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome. Blood, 111, 624-632.
Ferraris, J.R., Ferraris, V., Acquier, A.B., Sorroche, P.B., Saez, M.S., Ginaca, A. & Mendez, C.F. (2015). Activation of the alternative pathway of complement during the acute phase of typical haemolytic uraemic syndrome. Clin Exp Immunol, 181, 118-125.
Griener, T.P., Mulvey, G.L., Marcato, P. & Armstrong, G.D. (2007). Differential binding of Shiga toxin 2 to human and murine neutrophils. J Med Microbiol, 56, 1423-1430.
Gyles, C.L. (1992). Escherichia coli cytotoxins and enterotoxins. Can J Microbiol, 38, 734-746.
Heyderman, R.S., Soriani, M. & Hirst, T.R. (2001). Is immune cell activation the missing link in the pathogenesis of post-diarrhoeal HUS? Trends Microbiol, 9, 262-266.
Hughes, A.K., Stricklett, P.K. & Kohan, D.E. (1998). Cytotoxic effect of Shiga toxin-1 on human proximal tubule cells. Kidney Int, 54, 426-437.
Jacewicz, M.S., Acheson, D.W., Binion, D.G., West, G.A., Lincicome, L.L., Fiocchi, C. & Keusch, G.T. (1999). Responses of human intestinal microvascular endothelial cells to Shiga toxins 1 and 2 and pathogenesis of hemorrhagic colitis. Infection and immunity, 67, 1439-1444.
Jenkins, C., Willshaw, G.A., Evans, J., Cheasty, T., Chart, H., Shaw, D.J., Dougan, G., Frankel, G. & Smith, H.R. (2003). Subtyping of virulence genes in verocytotoxin-producing Escherichia coli (VTEC) other than serogroup O157 associated with disease in the United Kingdom. Journal of medical microbiology, 52, 941-947.
Johannes, L. & Romer, W. (2010). Shiga toxins--from cell biology to biomedical applications. Nat Rev Microbiol, 8, 105-116.
Jozsi, M., Licht, C., Strobel, S., Zipfel, S.L., Richter, H., Heinen, S., Zipfel, P.F. & Skerka, C. (2008). Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood, 111, 1512-1514.
Karch, H. (2001). The role of virulence factors in enterohemorrhagic Escherichia coli (EHEC)--associated hemolytic-uremic syndrome. Semin Thromb Hemost, 27, 207-213.
Keir, L.S., Marks, S.D. & Kim, J.J. (2012). Shigatoxin-associated hemolytic uremic syndrome: current molecular mechanisms and future therapies. Drug Des Devel Ther, 6, 195-208.
Lapeyraque, A.L., Malina, M., Fremeaux-Bacchi, V., et al. (2011). Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med, 364, 2561-2563.
Lee, M.S., Cherla, R.P. & Tesh, V.L. (2010). Shiga toxins: intracellular trafficking to the ER leading to activation of host cell stress responses. Toxins (Basel), 2, 1515-1535.
Lingwood, C.A. (1996). Role of verotoxin receptors in pathogenesis. Trends in microbiology, 4, 147-153.
Lingwood, C.A. (1999). Glycolipid receptors for verotoxin and Helicobacter pylori: role in pathology. Biochimica et biophysica acta, 1455, 375-386.
Lo, N.C., Turner, N.A., Cruz, M.A. & Moake, J. (2013). Interaction of Shiga toxin with the A-domains and multimers of von Willebrand Factor. J Biol Chem, 288, 33118-33123.
Locatelli, M., Buelli, S., Pezzotta, A., et al. (2014). Shiga toxin promotes podocyte injury in experimental hemolytic uremic syndrome via activation of the alternative pathway of complement. J Am Soc Nephrol, 25, 1786-1798.
Loos, S., Ahlenstiel, T., Kranz, B., et al. (2012). An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: presentation and short-term outcome in children. Clin Infect Dis, 55, 753-759.
Moore, I., Strain, L., Pappworth, I., et al. (2010). Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood, 115, 379-387.
Morigi, M., Buelli, S., Zanchi, C., Longaretti, L., Macconi, D., Benigni, A., Moioli, D., Remuzzi, G. & Zoja, C. (2006). Shigatoxin-induced endothelin-1 expression in cultured podocytes autocrinally mediates actin remodeling. Am J Pathol, 169, 1965-1975.
Morigi, M., Galbusera, M., Gastoldi, S., et al. (2011). Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis. J Immunol, 187, 172-180.
Muthing, J., Schweppe, C.H., Karch, H. & Friedrich, A.W. (2009). Shiga toxins, glycosphingolipid diversity, and endothelial cell injury. Thromb Haemost, 101, 252-264.
Nakao, H. & Takeda, T. (2000). Escherichia coli Shiga toxin. Journal of natural toxins, 9, 299-313.
Nolasco, L.H., Turner, N.A., Bernardo, A., Tao, Z., Cleary, T.G., Dong, J.F. & Moake, J.L. (2005). Hemolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers. Blood, 106, 4199-4209.
O'Brien, A.D. & Holmes, R.K. (1987). Shiga and Shiga-like toxins. Microbiol Rev, 51, 206-220.
O'Brien, A.D., LaVeck, G.D., Thompson, M.R. & Formal, S.B. (1982). Production of Shigella dysenteriae type 1-like cytotoxin by Escherichia coli. The Journal of infectious diseases, 146, 763-769.
O'Brien, A.D., Tesh, V.L., Donohue-Rolfe, A., Jackson, M.P., Olsnes, S., Sandvig, K., Lindberg, A.A. & Keusch, G.T. (1992). Shiga toxin: biochemistry, genetics, mode of action, and role in pathogenesis. Current topics in microbiology and immunology, 180, 65-94.
Obrig, T.G. (1997). Shiga toxin mode of action in E. coli O157:H7 disease. Front Biosci, 2, d635-642.
Oksjoki, R., Kovanen, P.T., Meri, S. & Pentikainen, M.O. (2007). Function and regulation of the complement system in cardiovascular diseases. Front Biosci, 12, 4696-4708.
Orth, D., Khan, A.B., Naim, A., et al. (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.
Palermo, M.S., Exeni, R.A. & Fernandez, G.C. (2009). Hemolytic uremic syndrome: pathogenesis and update of interventions. Expert Rev Anti Infect Ther, 7, 697-707.
Poolpol, K., Orth-Holler, D., Speth, C., Zipfel, P.F., Skerka, C., de Cordoba, S.R., Brockmeyer, J., Bielaszewska, M. & Wurzner, R. (2014). Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. Mol Immunol, 58, 77-84.
Rosales, A., Hofer, J., Zimmerhackl, L.B., Jungraithmayr, T.C., Riedl, M., Giner, T., Strasak, A., Orth-Holler, D., Würzner, R. & Karch, H. (2012). Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. Clin Infect Dis, 54, 1413-1421.
Ruggenenti, P., Noris, M. & Remuzzi, G. (2001). Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int, 60, 831-846.
Stahl, A.L., 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.
Stahl, A.L., Sartz, L., Nelsson, A., Bekassy, Z.D. & 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.
Takao, T., Tanabe, T., Hong, Y.M., Shimonishi, Y., Kurazono, H., Yutsudo, T., Sasakawa, C., Yoshikawa, M. & Takeda, Y. (1988). Identity of molecular structure of Shiga-like toxin I (VT1) from Escherichia coli O157:H7 with that of Shiga toxin. Microbial pathogenesis, 5, 57-69.
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.
Thurman, J.M., Marians, R., Emlen, W., et al. (2009). Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol, 4, 1920-1924.
van Setten, P.A., Monnens, L.A., Verstraten, R.G., van den Heuvel, L.P. & van Hinsbergh, V.W. (1996). Effects of verocytotoxin-1 on nonadherent human monocytes: binding characteristics, protein synthesis, and induction of cytokine release. Blood, 88, 174-183.
Zipfel, P.F., Mache, C., Muller, D., Licht, C., Wigger, M., Skerka, C. & European, D.-H.U.S.S.G. (2010). DEAP-HUS: deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome. Pediatr Nephrol, 25, 2009-2019.
Zipfel, P.F., Edey, M., Heinen, S., et al. (2007). Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome. PLoS genetics, 3, e41.
Zoja, C., Angioletti, S., Donadelli, R., et al. (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.
Zumbrun, S.D., Hanson, L., Sinclair, J.F., Freedy, J., Melton-Celsa, A.R., Rodriguez-Canales, J., Hanson, J.C. & O'Brien, A.D. (2010). Human intestinal tissue and cultured colonic cells contain globotriaosylceramide synthase mRNA and the alternate Shiga toxin receptor globotetraosylceramide. Infect Immun, 78, 4488-4499.
Beutin, L. & Martin, A. (2012). Outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in Germany causes a paradigm shift with regard to human pathogenicity of STEC strains. J Food Prot, 75, 408-418.
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. Infection and immunity, 62, 3337-3347.
Brigotti, M., Alfieri, R., Sestili, P., Bonelli, M., Petronini, P.G., Guidarelli, A., Barbieri, L., Stirpe, F. & Sperti, S. (2002). Damage to nuclear DNA induced by Shiga toxin 1 and ricin in human endothelial cells. FASEB J, 16, 365-372.
Brigotti, M., Carnicelli, D., Arfilli, V., et al. (2013). Identification of TLR4 as the receptor that recognizes Shiga toxins in human neutrophils. J Immunol, 191, 4748-4758.
Caillaud, C., Zaloszyc, A., Licht, C., Pichault, V., Fremeaux-Bacchi, V. & Fischbach, M. (2016). CFH gene mutation in a case of Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS). Pediatr Nephrol, 31, 157-161.
Caprioli, A., Morabito, S., Brugere, H. & Oswald, E. (2005). Enterohaemorrhagic Escherichia coli: emerging issues on virulence and modes of transmission. Vet Res, 36, 289-311.
Cohen, A., Madrid-Marina, V., Estrov, Z., Freedman, M.H., Lingwood, C.A. & Dosch, H.M. (1990). Expression of glycolipid receptors to Shiga-like toxin on human B lymphocytes: a mechanism for the failure of long-lived antibody response to dysenteric disease. Int Immunol, 2, 1-8.
De Petris, L., Patrick, J., Christen, E. & Trachtman, H. (2006). Urinary podocyte mRNA excretion in children with D+HUS: a potential marker of long-term outcome. Ren Fail, 28, 475-482.
Dragon-Durey, M.A., Blanc, C., Marliot, F., Loirat, C., Blouin, J., Sautes-Fridman, C., Fridman, W.H. & Fremeaux-Bacchi, V. (2009). The high frequency of complement factor H related CFHR1 gene deletion is restricted to specific subgroups of patients with atypical haemolytic uraemic syndrome. Journal of medical genetics, 46, 447-450.
Ehrlenbach, S., Rosales, A., Posch, W., Wilflingseder, D., Hermann, M., Brockmeyer, J., Karch, H., Satchell, S.C., Wurzner, R. & Orth-Holler, D. (2013). Shiga toxin 2 reduces complement inhibitor CD59 expression on human renal tubular epithelial and glomerular endothelial cells. Infect Immun, 81, 2678-2685.
Ergonul, Z., Hughes, A.K. & Kohan, D.E. (2003). Induction of apoptosis of human brain microvascular endothelial cells by shiga toxin 1. J Infect Dis, 187, 154-158.
Fang, C.J., Fremeaux-Bacchi, V., Liszewski, M.K., Pianetti, G., Noris, M., Goodship, T.H. & Atkinson, J.P. (2008). Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome. Blood, 111, 624-632.
Ferraris, J.R., Ferraris, V., Acquier, A.B., Sorroche, P.B., Saez, M.S., Ginaca, A. & Mendez, C.F. (2015). Activation of the alternative pathway of complement during the acute phase of typical haemolytic uraemic syndrome. Clin Exp Immunol, 181, 118-125.
Griener, T.P., Mulvey, G.L., Marcato, P. & Armstrong, G.D. (2007). Differential binding of Shiga toxin 2 to human and murine neutrophils. J Med Microbiol, 56, 1423-1430.
Gyles, C.L. (1992). Escherichia coli cytotoxins and enterotoxins. Can J Microbiol, 38, 734-746.
Heyderman, R.S., Soriani, M. & Hirst, T.R. (2001). Is immune cell activation the missing link in the pathogenesis of post-diarrhoeal HUS? Trends Microbiol, 9, 262-266.
Hughes, A.K., Stricklett, P.K. & Kohan, D.E. (1998). Cytotoxic effect of Shiga toxin-1 on human proximal tubule cells. Kidney Int, 54, 426-437.
Jacewicz, M.S., Acheson, D.W., Binion, D.G., West, G.A., Lincicome, L.L., Fiocchi, C. & Keusch, G.T. (1999). Responses of human intestinal microvascular endothelial cells to Shiga toxins 1 and 2 and pathogenesis of hemorrhagic colitis. Infection and immunity, 67, 1439-1444.
Jenkins, C., Willshaw, G.A., Evans, J., Cheasty, T., Chart, H., Shaw, D.J., Dougan, G., Frankel, G. & Smith, H.R. (2003). Subtyping of virulence genes in verocytotoxin-producing Escherichia coli (VTEC) other than serogroup O157 associated with disease in the United Kingdom. Journal of medical microbiology, 52, 941-947.
Johannes, L. & Romer, W. (2010). Shiga toxins--from cell biology to biomedical applications. Nat Rev Microbiol, 8, 105-116.
Jozsi, M., Licht, C., Strobel, S., Zipfel, S.L., Richter, H., Heinen, S., Zipfel, P.F. & Skerka, C. (2008). Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood, 111, 1512-1514.
Karch, H. (2001). The role of virulence factors in enterohemorrhagic Escherichia coli (EHEC)--associated hemolytic-uremic syndrome. Semin Thromb Hemost, 27, 207-213.
Keir, L.S., Marks, S.D. & Kim, J.J. (2012). Shigatoxin-associated hemolytic uremic syndrome: current molecular mechanisms and future therapies. Drug Des Devel Ther, 6, 195-208.
Lapeyraque, A.L., Malina, M., Fremeaux-Bacchi, V., et al. (2011). Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med, 364, 2561-2563.
Lee, M.S., Cherla, R.P. & Tesh, V.L. (2010). Shiga toxins: intracellular trafficking to the ER leading to activation of host cell stress responses. Toxins (Basel), 2, 1515-1535.
Lingwood, C.A. (1996). Role of verotoxin receptors in pathogenesis. Trends in microbiology, 4, 147-153.
Lingwood, C.A. (1999). Glycolipid receptors for verotoxin and Helicobacter pylori: role in pathology. Biochimica et biophysica acta, 1455, 375-386.
Lo, N.C., Turner, N.A., Cruz, M.A. & Moake, J. (2013). Interaction of Shiga toxin with the A-domains and multimers of von Willebrand Factor. J Biol Chem, 288, 33118-33123.
Locatelli, M., Buelli, S., Pezzotta, A., et al. (2014). Shiga toxin promotes podocyte injury in experimental hemolytic uremic syndrome via activation of the alternative pathway of complement. J Am Soc Nephrol, 25, 1786-1798.
Loos, S., Ahlenstiel, T., Kranz, B., et al. (2012). An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: presentation and short-term outcome in children. Clin Infect Dis, 55, 753-759.
Moore, I., Strain, L., Pappworth, I., et al. (2010). Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood, 115, 379-387.
Morigi, M., Buelli, S., Zanchi, C., Longaretti, L., Macconi, D., Benigni, A., Moioli, D., Remuzzi, G. & Zoja, C. (2006). Shigatoxin-induced endothelin-1 expression in cultured podocytes autocrinally mediates actin remodeling. Am J Pathol, 169, 1965-1975.
Morigi, M., Galbusera, M., Gastoldi, S., et al. (2011). Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis. J Immunol, 187, 172-180.
Muthing, J., Schweppe, C.H., Karch, H. & Friedrich, A.W. (2009). Shiga toxins, glycosphingolipid diversity, and endothelial cell injury. Thromb Haemost, 101, 252-264.
Nakao, H. & Takeda, T. (2000). Escherichia coli Shiga toxin. Journal of natural toxins, 9, 299-313.
Nolasco, L.H., Turner, N.A., Bernardo, A., Tao, Z., Cleary, T.G., Dong, J.F. & Moake, J.L. (2005). Hemolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers. Blood, 106, 4199-4209.
O'Brien, A.D. & Holmes, R.K. (1987). Shiga and Shiga-like toxins. Microbiol Rev, 51, 206-220.
O'Brien, A.D., LaVeck, G.D., Thompson, M.R. & Formal, S.B. (1982). Production of Shigella dysenteriae type 1-like cytotoxin by Escherichia coli. The Journal of infectious diseases, 146, 763-769.
O'Brien, A.D., Tesh, V.L., Donohue-Rolfe, A., Jackson, M.P., Olsnes, S., Sandvig, K., Lindberg, A.A. & Keusch, G.T. (1992). Shiga toxin: biochemistry, genetics, mode of action, and role in pathogenesis. Current topics in microbiology and immunology, 180, 65-94.
Obrig, T.G. (1997). Shiga toxin mode of action in E. coli O157:H7 disease. Front Biosci, 2, d635-642.
Oksjoki, R., Kovanen, P.T., Meri, S. & Pentikainen, M.O. (2007). Function and regulation of the complement system in cardiovascular diseases. Front Biosci, 12, 4696-4708.
Orth, D., Khan, A.B., Naim, A., et al. (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.
Palermo, M.S., Exeni, R.A. & Fernandez, G.C. (2009). Hemolytic uremic syndrome: pathogenesis and update of interventions. Expert Rev Anti Infect Ther, 7, 697-707.
Poolpol, K., Orth-Holler, D., Speth, C., Zipfel, P.F., Skerka, C., de Cordoba, S.R., Brockmeyer, J., Bielaszewska, M. & Wurzner, R. (2014). Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. Mol Immunol, 58, 77-84.
Rosales, A., Hofer, J., Zimmerhackl, L.B., Jungraithmayr, T.C., Riedl, M., Giner, T., Strasak, A., Orth-Holler, D., Würzner, R. & Karch, H. (2012). Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. Clin Infect Dis, 54, 1413-1421.
Ruggenenti, P., Noris, M. & Remuzzi, G. (2001). Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int, 60, 831-846.
Stahl, A.L., 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.
Stahl, A.L., Sartz, L., Nelsson, A., Bekassy, Z.D. & 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.
Takao, T., Tanabe, T., Hong, Y.M., Shimonishi, Y., Kurazono, H., Yutsudo, T., Sasakawa, C., Yoshikawa, M. & Takeda, Y. (1988). Identity of molecular structure of Shiga-like toxin I (VT1) from Escherichia coli O157:H7 with that of Shiga toxin. Microbial pathogenesis, 5, 57-69.
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.
Thurman, J.M., Marians, R., Emlen, W., et al. (2009). Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol, 4, 1920-1924.
van Setten, P.A., Monnens, L.A., Verstraten, R.G., van den Heuvel, L.P. & van Hinsbergh, V.W. (1996). Effects of verocytotoxin-1 on nonadherent human monocytes: binding characteristics, protein synthesis, and induction of cytokine release. Blood, 88, 174-183.
Zipfel, P.F., Mache, C., Muller, D., Licht, C., Wigger, M., Skerka, C. & European, D.-H.U.S.S.G. (2010). DEAP-HUS: deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome. Pediatr Nephrol, 25, 2009-2019.
Zipfel, P.F., Edey, M., Heinen, S., et al. (2007). Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome. PLoS genetics, 3, e41.
Zoja, C., Angioletti, S., Donadelli, R., et al. (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.
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2016-08-11
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