Fractalkine and CX3CR1 mediate leukocyte capture by endothelium in response to Shiga toxin

Journal of Immunology

Volumn 181, Issue 2, 2008, Pages 1460-1469

  Zanchi, Cristina ^a   Zoja, Carla ^a   Morigi, Marina ^a   Valsecchi, Federica ^a   Xue, Yan Liu ^b   Rottoli, Daniela ^a   Locatelli, Monica ^a   Buelli, Simona ^a   Pezzotta, Anna ^a   Mapelli, Paola ^a   Geelen, Joyce ^c   Remuzzi, Giuseppe ^a,d   Hawiger, Jacek ^b  

^a MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^b VANDERBILT UNIVERSITY   (United States)

^c RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^d OSPEDALI RIUNITI   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOKINE RECEPTOR CX3CR1; FRACTALKINE; I KAPPA B ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIPOPOLYSACCHARIDE; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE P38; PROTEIN TYROSINE KINASE; SHIGA TOXIN; SN 50; VEROTOXIN 2; VIRULENCE FACTOR; CHEMOKINE RECEPTOR; CX3CR1 PROTEIN, HUMAN; TRANSCRIPTION FACTOR AP 1;

ADENOVIRUS; ANIMAL CELL; ANIMAL MODEL; ARTICLE; C57BL 6 MOUSE; CELL INTERACTION; CELLULAR IMMUNITY; CONTROLLED STUDY; ENDOTHELIUM; ENDOTHELIUM CELL; ESCHERICHIA COLI; GLOMERULUS; HEMOLYTIC UREMIC SYNDROME; HUMAN; HUMAN CELL; INHIBITION KINETICS; LEUKOCYTE; LEUKOCYTE ADHERENCE; MOUSE; NONHUMAN; NUCLEAR IMPORT; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; UPREGULATION; ANIMAL; C57BL MOUSE; CELL ADHESION; CELL CULTURE; CYTOLOGY; DISEASE MODEL; ESCHERICHIA COLI O157; IMMUNOLOGY; MALE; METABOLISM; MICROBIOLOGY; SIGNAL TRANSDUCTION; VASCULARIZATION;

ANIMALS; CELL ADHESION; CELLS, CULTURED; CHEMOKINE CX3CL1; DISEASE MODELS, ANIMAL; ENDOTHELIAL CELLS; ESCHERICHIA COLI O157; HEMOLYTIC-UREMIC SYNDROME; HUMANS; KIDNEY GLOMERULUS; LEUKOCYTES; LIPOPOLYSACCHARIDES; MALE; MICE; MICE, INBRED C57BL; NF-KAPPA B; P38 MITOGEN-ACTIVATED PROTEIN KINASES; RECEPTORS, CHEMOKINE; SHIGA TOXIN 2; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTOR AP-1; UP-REGULATION;

EID: 49049104863     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.181.2.1460     Document Type: Article

References (73)

1. Remuzzi, G., and P. Ruggenenti. 1995. The hemolytic uremic syndrome. Kidney Int. 47: 2-19.
2. Arbus, G. S. 1997. Association of verotoxin-producing E. coli and verotoxin with hemolytic uremic syndrome. Kidney Int. Suppl. 58: S91-S96.
3. Ray, P. E., and X. H. Liu. 2001. Pathogenesis of Shiga toxin-induced hemolytic uremic syndrome. Pediatr. Nephrol. 16: 823-839. (Pubitemid 32895613)
4. Tarr, P. I., C. A. Gordon, and W. L. Chandler. 2005. Shiga-toxin- producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365: 1073-1086. (Pubitemid 40386785)
5. Riley, L. W., R. S. Remis, S. D. Helgerson, H. B. McGee, J. G. Wells, B. R. Davis, R. J. Hebert, E. S. Olcott, L. M. Johnson, N. T. Hargrett, et al. 1983. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N. Engl. J. Med. 308: 681-685.
6. Rangel, J. M., P. H. Sparling, C. Crowe, P. M. Griffin, and D. L. Swerdlow. 2005. Epidemiology of Escherichia coli O157:H7 outbreaks, United States, 1982-2002. Emerg. Infect Dis. 11: 603-609. (Pubitemid 40462912)
7. Mead, P. S., L. Slutsker, V. Dietz, L. F. McCaig, J. S. Bresee, C. Shapiro, P. M. Griffin, and R. V. Tauxe. 1999. Food-related illness and death in the United States. Emerg. Infect Dis. 5: 607-625. (Pubitemid 29493763)
8. Boyce, T. G., D. L. Swerdlow, and P. M. Griffin. 1995. Escherichia coli O157:H7 and the hemolytic-uremic syndrome. N. Engl. J. Med. 333: 364-368.
9. Donnenberg, M. S., and T. S. Whittam. 2001. Pathogenesis and evolution of virulence in enteropathogenic and enterohemorrhagic Escherichia coli. J. Clin. Invest. 107: 539-548.
10. O'Loughlin, E. V., and R. M. Robins-Browne. 2001. Effect of Shiga toxin and Shiga-like toxins on eukaryotic cells. Microbes Infect. 3: 493-507.
11. Sperandio, V., A. G. Torres, B. Jarvis, J. P. Nataro, and J. B. Kaper. 2003. Bacteria-host communication: the language of hormones. Proc. Natl. Acad. Sci. USA 100: 8951-8956.
12. Perna, N. T., G. Plunkett, 3rd, V. Burland, B. Mau, J. D. Glasner, D. J. Rose, G. F. Mayhew, P. S. Evans, J. Gregor, H. A. Kirkpatrick, et al. 2001. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409: 529-533.
13. Whale, A. D., J. Garmendia, T. A. Gomes, and G. Frankel. 2006. A novel category of enteropathogenic Escherichia coli simultaneously utilizes the Nck and TccP pathways to induce actin remodelling. Cell. Microbiol. 8: 999-1008.
14. Remuzzi, G., P. Ruggenenti, and T. Bertani. 1994. Thrombotic microangiopathy. In Renal Pathology with Clinical and Functional Correlations, 2nd Ed. C. C. Tisher and B. M. Brenner, eds. J. B. Lippincott, Philadelphia, pp. 1154-1184.
15. Siegler, R. L. 1994. Spectrum of extrarenal involvement in postdiarrheal hemolytic- uremic syndrome. J. Pediatr. 125: 511-518. (Pubitemid 24318419)
16. 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. (Pubitemid 23222039)
17. Morigi, M., G. Micheletti, M. Figliuzzi, B. Imberti, M. A. Karmali, A. Remuzzi, G. Remuzzi, and C. Zoja. 1995. Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions. Blood 86: 4553-4558.
18. Forsyth, K. D., A. C. Simpson, M. M. Fitzpatrick, T. M. Barratt, and R. J. Levinsky. 1989. Neutrophil-mediated endothelial injury in haemolytic uraemic syndrome. Lancet II: 411-414. (Pubitemid 19195959)
19. 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-κB dependent up-regulation of IL-8 and MCP-1. Kidney Int. 62: 846-856.
20. 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.
21. Guessous, F., M. Marcinkiewicz, R. Polanowska-Grabowska, S. Kongkhum, D. Heatherly, T. Obrig, and A. R. Gear. 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. (Pubitemid 41740321)
22. Thorpe, C. M., B. P. Hurley, L. L. Lincicome, M. S. Jacewicz, G. T. Keusch, and D. W. Acheson. 1999. Shiga toxins stimulate secretion of interleukin-8 from intestinal epithelial cells. Infect. Immun. 67: 5985-5993. (Pubitemid 29508128)
23. Inward, C. D., A. J. Howie, M. M. Fitzpatrick, F. Rafaat, D. V. Milford, and C. M. Taylor. 1997. Renal histopathology in fatal cases of diarrhoea-associated haemolytic uraemic syndrome. British Association for Paediatric Nephrology. Pediatr. Nephrol. 11: 556-559.
24. 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 patients with hemolytic uremic syndrome. Pediatr. Res. 43: 759-767.
25. Bazan, J. F., K. B. Bacon, G. Hardiman, W. Wang, K. Soo, D. Rossi, D. R. Greaves, A. Zlotnik, and T. J. Schall. 1997. A new class of membranebound chemokine with a CX3C motif. Nature 385: 640-644.
26. Umehara, H., E. T. Bloom, T. Okazaki, Y. Nagano, O. Yoshie, and T. Imai. 2004. Fractalkine in vascular biology: from basic research to clinical disease. Arterioscler. Thromb. Vasc. Biol. 24: 34-40. (Pubitemid 38082409)
27. Imaizumi, T., T. Matsumiya, K. Fujimoto, K. Okamoto, X. Cui, U. Ohtaki, H. Yoshida, and K. Satoh. 2000. Interferon-γ stimulates the expression of CX3CL1/fractalkine in cultured human endothelial cells. Tohoku J. Exp. Med. 192: 127-139. (Pubitemid 33621585)
28. Harrison, J. K., Y. Jiang, S. Chen, Y. Xia, D. Maciejewski, R. K. McNamara, W. J. Streit, M. N. Salafranca, S. Adhikari, D. A. Thompson, et al. 1998. Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc. Natl. Acad. Sci. USA 95: 10896-10901.
29. Black, R. A., and J. M. White. 1998. ADAMs: focus on the protease domain. Curr. Opin. Cell Biol. 10: 654-659.
30. Imai, T., K. Hieshima, C. Haskell, M. Baba, M. Nagira, M. Nishimura, M. Kakizaki, S. Takagi, H. Nomiyama, T. J. Schall, and O. Yoshie. 1997. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91: 521-530. (Pubitemid 27508241)
31. Fong, A. M., L. A. Robinson, D. A. Steeber, T. F. Tedder, O. Yoshie, T. Imai, and D. D. Patel. 1998. Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow. J. Exp. Med. 188: 1413-1419.
32. Goda, S., T. Imai, O. Yoshie, O. Yoneda, H. Inoue, Y. Nagano, T. Okazaki, H. Imai, E. T. Bloom, N. Domae, and H. Umehara. 2000. CX3C-chemokine, fractalkine-enhanced adhesion of THP-1 cells to endothelial cells through integrin- dependent and -independent mechanisms. J. Immunol. 164: 4313-4320. (Pubitemid 30215094)
33. Haskell, C. A., M. D. Cleary, and I. F. Charo. 1999. Molecular uncoupling of fractalkine-mediated cell adhesion and signal transduction: rapid flow arrest of CX3CR1-expressing cells is independent of G-protein activation. J. Biol. Chem. 274: 10053-10058. (Pubitemid 129518289)
34. Ramos, M. V., G. C. Fernandez, N. Patey, P. Schierloh, R. Exeni, I. Grimoldi, G. Vallejo, C. Elias-Costa, M. Del Carmen Sasiain, H. Trachtman, et al. 2007. Involvement of the fractalkine pathway in the pathogenesis of childhood hemolytic uremic syndrome. Blood 109: 2438-2445. (Pubitemid 46425886)
35. Palermo, M., F. Alves-Rosa, C. Rubel, G. C. Fernandez, G. Fernandez-Alonso, F. Alberto, M. Rivas, and M. Isturiz. 2000. Pretreatment of mice with lipopolysaccharide (LPS) or IL-1β exerts dose-dependent opposite effects on Shiga toxin-2 lethality. Clin. Exp. Immunol. 119: 77-83. (Pubitemid 30064594)
36. Ikeda, M., S. Ito, and M. Honda. 2004. Hemolytic uremic syndrome induced by lipopolysaccharide and Shiga-like toxin. Pediatr. Nephrol. 19: 485-489. (Pubitemid 38594284)
37. Keepers, T. R., M. A. Psotka, L. K. Gross, and T. G. Obrig. 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.
38. van Setten, P. A., V. W. van Hinsbergh, T. J. van der Velden, N. C. van de Kar, M. Vermeer, J. D. Mahan, K. J. Assmann, L. P. van den Heuvel, and L. A. Monnens. 1997. Effects of TNF α on verocytotoxin cytotoxicity in purified human glomerular microvascular endothelial cells. Kidney Int. 51: 1245-1256.
39. Morigi, M., S. Buelli, C. Zanchi, L. Longaretti, D. Macconi, A. Benigni, D. Moioli, G. Remuzzi, and C. Zoja. 2006. Shiga toxin-induced endothelin-1 expression in cultured podocytes autocrinally mediates actin remodeling. Am. J. Pathol. 169: 1965-1975. (Pubitemid 351181958)
40. Morigi, M., C. Zoja, M. Figliuzzi, M. Foppolo, G. Micheletti, M. Bontempelli, M. Saronni, G. Remuzzi, and A. Remuzzi. 1995. Fluid shear stress modulates surface expression of adhesion molecules by endothelial cells. Blood 85: 1696-1703.
41. Katagiri, Y. U., T. Mori, H. Nakajima, C. Katagiri, T. Taguchi, T. Takeda, N. Kiyokawa, and J. Fujimoto. 1999. Activation of Src family kinase yes induced by Shiga toxin binding to globotriaosyl ceramide (Gb3/CD77) in low density, detergent-insoluble microdomains. J. Biol. Chem. 274: 35278-35282.
42. 2+ increase in Vero cells. FEBS Lett. 485: 94-98.
43. Lin, Y. Z., S. Y. Yao, R. A. Veach, T. R. Torgerson, and J. Hawiger. 1995. Inhibition of nuclear translocation of transcription factor NF-κB by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. J. Biol. Chem. 270: 14255-14258.
44. Torgerson, T. R., A. D. Colosia, J. P. Donahue, Y. Z. Lin, and J. Hawiger. 1998. Regulation of NF-κB, AP-1, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-κB p50. J. Immunol. 161: 6084-6092.
45. Liu, X. Y., D. Robinson, R. A. Veach, D. Liu, S. Timmons, R. D. Collins, and J. Hawiger. 2000. Peptide-directed suppression of a pro-inflammatory cytokine response. J. Biol. Chem. 275: 16774-16778.
46. Wrighton, C. J., R. Hofer-Warbinek, T. Moll, R. Eytner, F. H. Bach, and R. de Martin. 1996. Inhibition of endothelial cell activation by adenovirus-mediated expression of IκBα, an inhibitor of the transcription factor NF-κB. J. Exp. Med. 183: 1013-1022. (Pubitemid 26114800)
47. Viedt, C., R. Dechend, J. Fei, G. M. Hansch, J. Kreuzer, and S. R. Orth. 2002. MCP-1 induces inflammatory activation of human tubular epithelial cells: involvement of the transcription factors, nuclear factor-κB and activating protein-1. J. Am. Soc. Nephrol. 13: 1534-1547. (Pubitemid 34579243)
48. Lawrence, M. B., L. V. McIntire, and S. G. Eskin. 1987. Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion. Blood 70: 1284-1290. (Pubitemid 18026127)
49. Remuzzi, A., B. M. Brenner, V. Pata, G. Tebaldi, R. Mariano, A. Belloro, and G. Remuzzi. 1992. Three-dimensional reconstructed glomerular capillary network: blood flow distribution and local filtration. Am. J. Physiol. 263: F562-F572.
50. Donadelli, R., C. Zanchi, M. Morigi, S. Buelli, C. Batani, S. Tomasoni, D. Corna, D. Rottoli, A. Benigni, M. Abbate, et al. 2003. Protein overload induces fractalkine upregulation in proximal tubular cells through nuclear factor κB- and p38 mitogen-activated protein kinase-dependent pathways. J. Am. Soc. Nephrol. 14: 2436-2446. (Pubitemid 37169329)
51. Heyderman, R. S., M. Soriani, and T. R. Hirst. 2001. Is immune cell activation the missing link in the pathogenesis of post-diarrhoeal HUS? Trends Microbiol. 9: 262-266.
52. Nakamura, A., E. J. Johns, A. Imaizumi, Y. Yanagawa, and T. Kohsaka. 2001. Activation of β2-adrenoceptor prevents Shiga toxin 2-induced TNF-α gene transcription. J. Am. Soc. Nephrol. 12: 2288-2299. (Pubitemid 33021106)
53. Garcia, G. E., Y. Xia, S. Chen, Y. Wang, R. D. Ye, J. K. Harrison, K. B. Bacon, H. G. Zerwes, and L. Feng. 2000. NF-κB-dependent fractalkine induction in rat aortic endothelial cells stimulated by IL-1β, TNF-α, and LPS. J. Leukocyte Biol. 67: 577-584.
54. Ahn, S. Y., C. H. Cho, K. G. Park, H. J. Lee, S. Lee, S. K. Park, I. K. Lee, and G. Y. Koh. 2004. Tumor necrosis factor-α induces fractalkine expression preferentially in arterial endothelial cells and mithramycin A suppresses TNF-α-induced fractalkine expression. Am. J. Pathol. 164: 1663-1672.
55. Chen, Y. M., S. L. Lin, C. W. Chen, W. C. Chiang, T. J. Tsai, and B. S. Hsieh. 2003. Tumor necrosis factor-α stimulates fractalkine production by mesangial cells and regulates monocyte transmigration: down-regulation by cAMP. Kidney Int. 63: 474-486.
56. Hawiger, J. 2001. Innate immunity and inflammation: a transcriptional paradigm. Immunol. Res. 23: 99-109. (Pubitemid 32575352)
57. Veach, R. A., D. Liu, S. Yao, Y. Chen, X. Y. Liu, S. Downs, and J. Hawiger. 2004. Receptor/transporter-independent targeting of functional peptides across the plasma membrane. J. Biol. Chem. 279: 11425-11431.
58. 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.
59. Coratelli, P., E. Buongiorno, and G. Passavanti. 1988. Endotoxemia in hemolytic uremic syndrome. Nephron 50: 365-367.
60. Bitzan, M., E. Moebius, K. Ludwig, D. E. Muller-Wiefel, J. Heesemann, and H. Karch. 1991. High incidence of serum antibodies to Escherichia coli O157 lipopolysaccharide in children with hemolytic-uremic syndrome. J. Pediatr. 119: 380-385.
61. Clayton, F., T. J. Pysher, R. Lou, D. E. Kohan, N. D. Denkers, V. L. Tesh, F. B. Taylor, Jr., and R. L. Siegler. 2005. Lipopolysaccharide upregulates renal Shiga toxin receptors in a primate model of hemolytic uremic syndrome. Am. J. Nephrol. 25: 536-540. (Pubitemid 41816047)
62. Roche, J. K., T. R. Keepers, L. K. Gross, R. M. Seaner, and T. G. Obrig. 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.
63. Keepers, T. R., L. K. Gross, and T. G. Obrig. 2007. Monocyte chemoattractant protein 1, macrophage inflammatory protein 1α, and RANTES recruit macrophages to the kidney in a mouse model of hemolytic-uremic syndrome. Infect. Immun. 75: 1229-1236.
64. McDermott, D. H., J. P. Halcox, W. H. Schenke, M. A. Waclawiw, M. N. Merrell, N. Epstein, A. A. Quyyumi, and P. M. Murphy. 2001. Association between polymorphism in the chemokine receptor CX3CR1 and coronary vascular endothelial dysfunction and atherosclerosis. Circ. Res. 89: 401-407.
65. Moatti, D., S. Faure, F. Fumeron, W. Amara Mel, P. Seknadji, D. H. McDermott, P. Debre, M. C. Aumont, P. M. Murphy, D. de Prost, and C. Combadiere. 2001. Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease. Blood 97: 1925-1928. (Pubitemid 32239068)
66. McDermott, D. H., A. M. Fong, Q. Yang, J. M. Sechler, L. A. Cupples, M. N. Merrell, P. W. Wilson, R. B. D'Agostino, C. J. O'Donnell, D. D. Patel, and P. M. Murphy. 2003. Chemokine receptor mutant CX3CR1-M280 has impaired adhesive function and correlates with protection from cardiovascular disease in humans. J. Clin. Invest. 111: 1241-1250.
67. Callera, G. E., R. M. Touyz, R. C. Tostes, A. Yogi, Y. He, S. Malkinson, and E. L. Schiffrin. 2005. Aldosterone activates vascular p38MAP kinase and NADPH oxidase via c-Src. Hypertension 45: 773-779.
68. Davis, M. E., I. M. Grumbach, T. Fukai, A. Cutchins, and D. G. Harrison. 2004. Shear stress regulates endothelial nitric-oxide synthase promoter activity through nuclear factor κB binding. J. Biol. Chem. 279: 163-168.
69. Carter, A. B., K. L. Knudtson, M. M. Monick, and G. W. Hunninghake. 1999. The p38 mitogen-activated protein kinase is required for NF-κB-dependent gene expression: the role of TATA-binding protein (TBP). J. Biol. Chem. 274: 30858-30863. (Pubitemid 129576833)
70. O'Neill, L. A., and A. G. Bowie. 2007. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol. 7: 353-364.
71. Matsuzawa, A., and H. Ichijo. 2008. Redox control of cell fate by MAP kinase: physiological roles of ASK1-MAP kinase pathway in stress signaling. Biochim. Biophys. Acta. In press.
72. Cherla, R. P., S. Y. Lee, P. L. Mees, and V. L. Tesh. 2006. Shiga toxin 1-induced cytokine production is mediated by MAP kinase pathways and translation initiation factor eIF4E in the macrophage-like THP-1 cell line. J. Leukocyte Biol. 79: 397-407.
73. Stone, M. K., G. L. Kolling, M. H. Lindner, and T. G. Obrig. 2008. p38 mitogenactivated protein kinase mediates lipopolysaccharide and tumor necrosis factor α induction of Shiga toxin 2 sensitivity in human umbilical vein endothelial cells. Infect. Immun. 76: 1115-1121.