Shiga toxin 2 and lipopolysaccharide induce human microvascular endothelial cells to release chemokines and factors that stimulate platelet function

Infection and Immunity

Volumn 73, Issue 12, 2005, Pages 8306-8316

  Guessous, Fadila ^a   Marcinkiewicz, Marek ^a   Polanowska Grabowska, Renata ^a   Kongkhum, Sudawadee ^a,b   Heatherly, Daniel ^a,c   Obrig, Tom ^a   Gear, Adrian R L ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

^b THAMMASAT UNIVERSITY   (Thailand)

^c RD 1 Box 158 ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE DIPHOSPHATE; BACTERIUM LIPOPOLYSACCHARIDE; CHEMOKINE; INDOMETACIN; INTERLEUKIN 8; MACROPHAGE DERIVED CHEMOKINE; PADGEM PROTEIN; PROSTAGLANDIN SYNTHASE; RANTES; STROMAL CELL DERIVED FACTOR 1ALPHA; STROMAL CELL DERIVED FACTOR 1BETA; THYMUS AND ACTIVATION REGULATED CHEMOKINE; VEROTOXIN 2;

ARTICLE; CELL CULTURE; CELL INTERACTION; CONTROLLED STUDY; CULTURE MEDIUM; ENZYME INHIBITION; ESCHERICHIA COLI O157; EVALUATION; HEMOLYTIC UREMIC SYNDROME; HUMAN; HUMAN CELL; IMMUNOASSAY; MICROVASCULATURE; PRIORITY JOURNAL; PROTEIN FUNCTION; SUPERNATANT; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION; THROMBOSIS; VASCULAR ENDOTHELIUM;

BLOOD PLATELETS; CAPILLARIES; CELLS, CULTURED; CHEMOKINES; COCULTURE TECHNIQUES; ENDOTHELIAL CELLS; ENDOTHELIUM, VASCULAR; ESCHERICHIA COLI O157; HUMANS; LIPOPOLYSACCHARIDES; P-SELECTIN; PLATELET AGGREGATION; SEROTONIN; SHIGA-LIKE TOXIN II;

EID: 28444432684     PISSN: 00199567     EISSN: None     Source Type: Journal    
DOI: 10.1128/IAI.73.12.8306-8316.2005     Document Type: Article

References (88)

1. Abi-Younes, S., A. Sauty, F. Mach, G. K. Sukhova, P. Libby, and A. D. Luster. 2000. The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques. Circ. Res. 86:131-138.
2. Ades, E. W., F. J. Candal, R. A. Swerlick, V. G. George, S. Summers, D. C. Bosse, and T. J. Lawley. 1992. HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J. Investig. Dermatol. 99:683-690.
3. Ahuja, S. K., and P. M. Murphy. 1996. The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interieukin-8 receptor. J. Biol. Chem. 271:20545-20550.
4. Andreoli, S. P. 1999. The pathophysiology of the hemolytic uremic syndrome. Curr. Opin. Nephrol. Hypertens. 8:459-464.
5. Appiani, A. C., A. Edefonti, A. Bettinelli, M. M. Cossu, M. L. Paracchini, and E. Rossi. 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.
6. Ashman, N., M. G. Macey, S. L. Fan, U. Azam, and M. M. Yaqoob. 2003. Increased platelet-monocyte aggregates and cardiovascular disease in end-stage renal failure patients. Nephrol. Dial. Transplant. 18:2088-2096.
7. Binion, D. G., G. A. West, K. Ina, N. P. Ziats, S. N. Emancipator, and C. Fiocchi. 1997. Enhanced leukocyte binding by intestinal microvascular endothelial cells in inflammatory bowel disease. Gastroenterology 112:1895-1907.
8. Blackall, D. P., and M. B. Marques. 2004. Hemolytic uremic syndrome revisited: Shiga toxin, factor H, and fibrin generation. Am. J. Clin. Pathol. 121(Suppl.):S81-S88.
9. Boerlin, P., S. A. McEven, F. Boerlin-Petzold, J. B. Wilson, V. Johnson, and C. L. Gyles. 1999. Associations between virulence factors of Shiga toxin-producing Escherichia coli and disease in humans. J. Clin. Microbiol. 37:497-503.
10. Bokarewa, M. I., J. H. Morrissey, and A. Tarkowski. 2002. Tissue factor as a proinflammatory agent. Arthritis Res. 4:190-195.
11. Borsch-Haubold, A. G., F. Bartoli, J. Asselin, T. Dudler, R. M. Kramer, R. Apitz-Castro, S. P. Watson, and M. H. Gelb. 1998. Identification of the phosphorylation sites of cytosolic phospholipase A2 in agonist-stimulated human platelets and HeLa cells. J. Biol. Chem. 273:4449-4458.
12. Brass, L. F., and M. Molino. 1997. Protease-activated G protein-coupled receptors on human platelets and endothelial cells. Thromb. Haemostasis 78:234-241.
13. Chandler, W. L., S. Jelacic, D. R. Boster, M. A. Ciol, G. D. Williams, S. L. Watkins, T. Igarashi, and P. I. Tarr. 2002. Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome. N. Engl. J. Med. 346:23-32.
14. Clemetson, K. J., J. M. Clemetson, A. E. Proudfoot, C. A. Power, M. Baggiolini, and T. N. Wells. 2000. Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets. Blood 96:4046-4054.
15. Corrigan, J. J., Jr., and F. G. Boineau. 2001. Hemolytic-uremic syndrome. Pediatr. Rev. 22:365-369.
16. Coulon, L., C. Calzada, P. Moulin, E. Vericel, and M. Lagarde. 2003. Activation of p38 mitogen-activated protein kinase/cytosolic phospholipase A2 cascade in hydroperoxide-stressed platelets. Free Radic. Biol. Med. 35:616-625.
17. Del Conde, I., C. N. Shrimpton, P. Thiagarajan, and J. A. Lopez. 2005. Tissue factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106:1604-1611.
18. Ebnet, K., and D. Vestweber. 1999. Molecular mechanisms that control leukocyte extravasation: the selectins and the chemokines. Histochem. Cell. Biol. 112:1-23.
19. Eisenhauer, P. B., P. Chaturvedi, R. E. Fine, A. J. Ritchie, J. S. Pober, T. G. Cleary, and D. S. Newburg. 2001. Tumor necrosis factor alpha increases human cerebral endothelial cell Gb3 and sensitivity to Shiga toxin. Infect. Immun. 69:1889-1894.
20. Faure, E., O. Equils, P. A. Sieling, L. Thomas, F. X. Zhang, C. J. Kirschning, N. Polentarutti, M. Muzio, and M. Arditi. 2000. Bacterial lipopolysaccharide activates NF-kappaB through Toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J. Biol. Chem. 275:11058-11063.
21. Freedman, J. E., and J. Loscalzo. 2002. Platelet-monocyte aggregates: bridging thrombosis and inflammation. Circulation 105:2130-2132.
22. Furie, B., and B. C. Furie. 1997. Leukocyte crosstalk at the vascular wall. Thromb. Haemostasis 78:306-309.
23. Furie, B., B. C. Furie, and R. Flaumenhaft. 2001. A journey with platelet P-selectin: the molecular basis of granule secretion, signalling and cell adhesion. Thromb. Haemostasis 86:214-221.
24. Furman, M. I., S. E. Benoit, M. R. Barnard, C. R. Valeri, M. L. Borbone, R. C. Becker, H. B. Hechtman, and A. D. Michelson. 1998. Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J. Am. Coll. Cardiol. 31:352-358.
25. Gawaz, M., K. Brand, T. Dickfeld, G. Pogatsa-Murray, S. Page, C. Bogner, W. Koch, A. Schomig, and F. Neumann. 2000. Platelets induce alterations of chemotactic and adhesive properties of endothelial cells mediated through an interleukin-1-dependent mechanism. Implications for atherogenesis. Atherosclerosis 148:75-85.
26. Gear, A. R. 1982. Rapid reactions of platelets studied by a quenched-flow approach: aggregation kinetics. J. Lab. Clin. Med. 100:866-886.
27. Gear, A. R., and D. Camerini. 2003. Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation 10:335-350.
28. Gear, A. R., S. Suttitanamongkol, D. Viisoreanu, R. K. Polanowska-Grabowska, S. Raha, and D. Camerini. 2001. Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet function. Blood 97:937-945.
29. Ghosh, S. A., R. K. Polanowska-Grabowska, J. Fujii, T. Obrig, and A. R. Gear. 2004. Shiga toxin binds to activated platelets. J. Thromb. Haemostasis 2:499-506.
30. Guessous, F., M. Marcinkiewicz, R. Polanowska-Grabowska, T. R. Keepers, T. Obrig, and A. R. L. Gear. STX2 and LPS cause monocytic THP-1 cells to release factors which activate platelet function. Thrombos. Haemostasis, in press.
31. Gupta, S. K., P. G. Lysko, K. Pillarisetti, E. Ohlstein, and J. M. Stadel. 1998. Chemokine receptors in human endothelial cells. Functional expression of CXCR4 and its transcriptional regulation by inflammatory cytokines. J. Biol. Chem. 273:4282-4287.
32. Harrison, L. M., C. van den Hoogen, W. C. van Haaften, and V. L. Tesh. 2005. Chemokine expression in the monocytic cell line THP-1 in response to purified Shiga toxin 1 and/or lipopolysaccharides. Infect. Immun. 73:403-412.
33. Harrison, L. M., W. C. E. van Haaften, and V. L. Tesh. 2004. Regulation of proinflammatory cytokine expression by Shiga toxin 1 and/or lipopolysaccharides in the human monocytic cell line THP-1. Infect. Immun. 72:2618-2627.
34. Hefner, Y., A. G. Borsch-Haubold, M. Murakami, J. I. Wilde, S. Pasquet, D. Schieltz, F. Ghomashchi, J. R. Yates III, C. G. Armstrong, A, Paterson, P. Cohen, R. Fukunaga, T. Hunter, I. Kudo, S. P. Watson, and M. H. Gelb. 2000. Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases. J. Biol. Chem. 275:37542-37551.
35. Hughes, A. K., D. I. Schmid, and D. E. Kohan. 2002. Sex steroids do not affect Shiga toxin cytotoxicity on human renal tubular or glomerular cells. BMC Nephrol. 3:6.
36. Huo, Y., and K. F. Ley. 2004. Role of platelets in the development of atherosclerosis. Trends Cardiovasc. Med. 14:18-22.
37. Huo, Y., A. Schober, S. B. Forlow, D. F. Smith, M. C. Hyman, S. Jung, D. R. Littman, C. Weber, and K. Ley. 2003. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat. Med. 9:61-67.
38. Jones, G. D., D. J. Carty, D. L. Freas, J. T. Spears, and A. R. Gear. 1989. Effects of separate proteolytic and high-affinity binding activities of human thrombin on rapid platelet activation. A quenched-flow study. Biochem. J. 262:611-616.
39. Kamitsuji, H., K. Nonami, T. Murakami, N. Ishikawa, A. Nakayama, and Y. Umeki. 2000. Elevated tissue factor circulating levels in children with hemolytic uremic syndrome caused by verotoxin-producing E. coli. Clin. Nephrol. 53:319-324.
40. Kaplan, B. S., T. G. Cleary, and T. G. Obrig. 1990. Recent advances in understanding the pathogenesis of the hemolytic uremic syndromes. Pediatr. Nephrol. 4:276-283.
41. Kaplan, B. S., K. E. Meyers, and S. L. Schulman. 1998. The pathogenesis and treatment of hemolytic uremic syndrome. J. Am. Soc. Nephrol. 9:1126-1133.
42. Karpman, D., D. Papadopoulou, K. Nilsson, A. C. Sjogren, C. Mikaelsson, and S. Lethagen. 2001. Platelet activation by Shiga toxin and circulatory factors as a pathogenetic mechanism in the hemolytic uremic syndrome. Blood 97:3100-3108.
43. Koster, F., J. Levin, L. Walker, K. S. Tung, R. H. Gilman, M. M. Rahaman, M. A. Majid, S. Islam, and R. C. Williams, Jr. 1978. Hemolytic-uremic syndrome after shigellosis. Relation to endotoxemia and circulating immune complexes. N. Engl. J. Med. 298:927-933.
44. Koster, F. T., V. Boonpucknavig, S. Sujaho, R. H. Gilman, and M. M. Rahaman. 1984. Renal histopathology in the hemolytic-uremic syndrome following shigellosis. Clin. Nephrol. 21:126-133.
45. Kowalska, M. A., M. Z. Ratajczak, M. Majka, J. Jin, S. Kunapuli, L. Brass, and M. Poncz. 2000. Stromal cell-derived factor-1 and macrophage-derived chemokine: two chemokines that activate platelets. Blood 96:50-57.
46. Kramer, R. M., and J. D. Sharp. 1995. Recent insights into the structure, function and biology of cPLA2. Agents Actions Suppl. 46:65-76.
47. Larsen, E., A. Celi, G. E. Gilbert, B. C. Furie, J. K. Erban, R. Bonfanti, D. D. Wagner, and B. Furie. 1989. PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 59:305-312.
48. Lingwood, C. A. 1996. Role of verotoxin receptors in pathogenesis. Trends Microbiol. 4:147-153.
49. Litauen, C., F. Proulx, M. M. Mariscalco, P. Robitaille, J. P. Turgeon, E. Orrbine, P. C. Rowe, P. N. McLaine, and E. Seidman. 1999. Circulating inflammatory cytokine levels in hemolytic uremic syndrome. Pediatr. Nephrol. 13:840-845.
50. Louise, C. B., and T. G. Obrig. 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.
51. Louise, C. B., and T. G. Obrig. 1991. Shiga toxin-associated hemolytic-uremic syndrome: combined cytotoxic effects of Shiga toxin, interleukin-1β, and tumor necrosis factor alpha on human vascular endothelial cells in vitro. Infect. Immun. 59:4173-4179.
52. Lova, P., S. Paganini, F. Sinigaglia, C. Balduini, and M. Torti. 2002. A Gi-dependent pathway is required for activation of the small GTPase Rap1B in human platelets. J. Biol. Chem. 277:12009-12015.
53. Maayani, S., T. Schwarz, B. Craddock-Royal, and T. M. Tagliente. 2001. Activation of the alpha(2A)-adrenoceptor mediates deceleration of the deaggregation component of the response to ADP or 5-HT in human platelets in vitro. Platelets 12:359-375.
54. Matsunaga, T., T. Nakajima, M. Sonoda, S. Kawai, J. Kobayashi, I. Inoue, A. Satomi, S. Katayama, A. Hara, S. Hokari, T. Honda, and T. Komoda. 1999. Reactive oxygen species as a risk factor in verotoxin-1-exposed rats. Biochem. Biophys. Res. Commun. 260:813-819.
55. Moake, J. L. 2002. Thrombotic microangiopathies. N. Engl. J. Med. 347:589-600.
56. Moake, J. L. 2002. Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. Arch. Pathol. Lab. Med. 126:1430-1433.
57. Morigi, M., M. Galbusera, E. Binda, B, Imberti, S. Gastoldi, A. Remuzzi, C. Zoja, and G. Remuzzi. 2001. Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress. Blood 98:1828-1835.
58. Noris, M., A. Benigni, R. Siegler, F. Gaspari, F, Casiraghi, M. L. Mancini, and G. Remuzzi. 1992. Renal prostacyclin biosynthesis is reduced in children with hemolytic-uremic syndrome in the context of systemic platelet activation. Am. J. Kidney Dis. 20:144-149.
59. Obrig, T. 1992. Pathogenesis of Shiga toxin (verotoxin)-induced endothelial cell injury, p. 405-419. In B. S. Kaplan, R. S. Throrapeter, and J. L. Moake (ed.), Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Marcel Dekker, New York, N.Y.
60. Obrig, T. G., P. J. Del Vecchio, M. A. Karmali, M. Petric, T. P. Moran, and T. K. Judge. 1987. Pathogenesis of haemolytic uraemic syndrome. Lancet 2:687.
61. Obrig, T. G., C. B. Louise, C. A. Lingwood, B. Boyd, L. Barley-Maloney, and T. O. Daniel. 1993. Endothelial heterogeneity in Shiga toxin receptors and responses. J. Biol. Chem. 268:15484-15488.
62. Osterud, B. 2003. The role of platelets in decrypting monocyte tissue factor. Dis. Month. 49:7-13.
63. Proudfoot, A. E., M. C. Peitsch, C. A. Power, B. Allet, J. J. Mermod, K. Bacon, and T. N. Wells. 1997. Structure and bioactivity of recombinant human CTAP-III and NAP-2. J. Protein Chem. 16:37-49.
64. Proudfoot, A. E., C. A. Power, A. Hoogewerf, M. O. Montjovent, F. Borlat, and T. N. Wells. 1995. Characterisation of the RANTES/MIP-1 alpha receptor (CC CKR-1) stably transfected in HEK 293 cells and the recombinant ligands. FEBS Lett. 376:19-23.
65. Ramegowda, B., and V. L. Tesh. 1996. Differentiation-associated toxin receptor modulation, cytokine production, and sensitivity to Shiga-like toxins in human monocytes and monocytic cell lines. Infect. Immun. 64:1173-1180.
66. Ray, P. E., and X. H. Liu. 2001. Pathogenesis of Shiga toxin-induced hemolytic uremic syndrome. Pediatr. Nephrol. 16:823-839.
67. Ruggenenti, P., M. Noris, and G. Remuzzi. 2001. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int. 60:831-846.
68. Schmid, D. I., and D. E. Kohan. 2001. Effect of shigatoxin-1 on arachidonic acid release by human gloraerular epithelial cells. Kidney Int. 60:1026-1036.
69. Shenkman, B., A. Brill, G. Brill, O. Lider, N. Savion, and D. Varon. 2004. Differential response of platelets to chemokines: RANTES non-competitively inhibits stimulatory effect of SDF-1alpha. J. Thromb. Haemostasis 2:154-160.
70. Simonini, A., M. Moscucci, D. W. Muller, E. R. Bates, F. D. Pagani, M. D. Burdick, and R. M. Stricter. 2000. IL-8 is an angiogenic factor in human coronary atherectomy tissue. Circulation 101:1519-1526.
71. Steen, V. M., H. Holmsen, and G. Aarbakke. 1993. The platelet-stimulating effect of adrenaline through alpha 2-adrenergic receptors requires simultaneous activation by a true stimulatory platelet agonist. Evidence that adrenaline per se does not induce human platelet activation in vitro. Thromb. Haemostasis 70:506-513.
72. Stricklett, P. K., A. K. Hughes, Z. Ergonul, and D. E. Kohan. 2002. Molecular basis for up-regulation by inflammatory cytokines of Shiga toxin 1 cytotoxicity and globotriaosylceramide expression. J. Infect. Dis. 186:976-982.
73. Strockbine, N. A., L. R. Marques, J. W. Newland, H. W. Smith, R. K. Holmes, and A. D. O'Brien. 1986. Two toxin-converting phages from Escherichia coli O157:H7 strain 933 encode antigenically distinct toxins with similar biologic activities. Infect. Immun. 53:135-140.
74. Suttitanamongkol, S., and A. R. Gear. 2001. ADP receptor antagonists inhibit platelet aggregation induced by the chemokines SDF-1, MDC and TARC. FEBS Lett. 490:84-87.
75. Tang, G., J. Yang, Y. Minemoto, and A, Lin. 2001. Blocking caspase-3-mediated proteolysis of IKKbeta suppresses TNF-alpha-induced apoptosis. Mol. Cell 8:1005-1016.
76. Tarr, P. I., C. A. Gordon, and W. L. Chandler. 2005. Shiga-toxin- producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365:1073-1086.
77. Tesh, V. L., J. A. Burris, J. W. Owens, V. M. Gordon, E. A. Wadolkowski, A. D. O'Brien, and J. E. Samuel. 1993. Comparison of the relative toxicities of Shiga-like toxins type I and type II for mice. Infect. Immun. 61:3392-3402.
78. Tesh, V. L., B. Ramegowda, and J. E. Samuel. 1994. Purified Shiga-like toxins induce expression of proinflammatory cytokines from murine peritoneal macrophages. Infect. Immun. 62:5085-5094.
79. Thorpe, C. M., W. E. Smith, B. P. Hurley, and D. W. Acheson. 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.
80. Tiffany, H. L., L. L. Lautens, J. L. Gao, J. Pease, M. Locati, C. Combadiere, W. Modi, T. I. Bonner, and P. M. Murphy. 1997. Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309. J. Exp. Med. 186:165-170.
81. Tonshoff, B., R. Momper, P. G. Kuhl, H. Schweer, K. Scharer, and H. W. Seyberth. 1990. Increased thromboxane biosynthesis in childhood hemolytic uremic syndrome. Kidney Int. 37:1134-1141.
82. van de Kar, N. C., L. A. Monnens, M. A. Karmali, and V. W. van Hinsbergh. 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.
83. Vandendries, E. R., B. C. Furie, and B. Furie. 2004. Role of P-selectin and PSGL-1 in coagulation and thrombosis. Thromb. Haemostasis 92:459-466.
84. van Setten, P. A., L. A. Monnens, R. G. Verstraten, L. P. van den Heuvel, and V. W. van Hinsbergh. 1996. Effects of verocytotoxin-1 on nonadherent human monocytes: binding characteristics, protein synthesis, and induction of cytokine release. Blood 88:174-183.
85. van Setten, P. A., V. W. van Hinsbergh, L. P. van den Heuvel, F. Preyers, H. B. Dijkman, K. J. Assmann, T. J. van der Velden, and L. A. Monnens. 1998. Monocyte chemoattractant protein-1 and interleukin-8 levels in urine and serum of patents with hemolytic uremic syndrome. Pediatr. Res. 43:759-767.
86. Viisoreanu, D., R. Polanowska-Grabowska, S. Suttitanamongkol, T. G. Obrig, and A. R. Gear. 2000. Human platelet aggregation is not altered by Shiga toxins 1 or 2. Thromb. Res. 98:403-410.
87. Walters, M. D., M. Levin, C. Smith, T. J. Nokes, R. M. Hardisty, M. J. Dillon, and T. M. Barratt. 1988. Intravascular platelet activation in the hemolytic uremic syndrome. Kidney Int. 33:107-115.
88. Zoja, C., S. Angioletti, R. Donadelli, C. Zanchi, S. Tomasoni, E. Binda, B. Imberti, M. te Loo, L. Monnens, G. Remuzzi, and M. Morigi. 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.