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Mechanisms of Staphylococcus aureus induced apoptosis of human endothelial cells

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Abstract

Staphylococcus aureus plays an important role in sepsis, pneumonia and wound infections. Here, we demonstrate that infection with several S. aureus strains results in apoptosis of human endothelial cells. S. aureus induced an activation of cellular caspases, the acid sphingomyelinase, a release of cytochrome c and a stimulation of Jun NH2-terminal kinase (JNK). The significance of these findings is indicated by a prevention of S. aureus triggered apoptosis of human cells deficient for ASM or upon genetic or pharmacological inhibition of JNK or caspases, respectively.

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References

  1. Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998; 339: 520-532.

    Google Scholar 

  2. Chesney PJ. Clinical aspects and spectrum of illness of toxic shock syndrome: Overview. Rev Infect Dis 1989; 11: S1-7.

    Google Scholar 

  3. Almeida RA, Matthews KR, Cifrian E, et al. Staphylococcus aureus invasion of bovine mammary epithelial cells. J Dairy Sci 1996; 79: 1021-1026.

    Google Scholar 

  4. Hamill RJ, Vann JM, Proctor RA. Phagocytosis of Staphylococcus aureus by cultured bovine aortic endothelial cells: Model for postadherence events in endovascular infections. Infect Immun 1986; 54: 833-836.

    Google Scholar 

  5. Ogawa SK, Yurberg ER, Hatcher VB, et al. Bacterial adherence to human endothelial cells in vitro. Infect Immun 1985; 50: 218-224.

    Google Scholar 

  6. Ellington JK, Reilly SS, Ramp WK, et al. Mechanisms of Staphylococcus aureus invasion of cultured osteoblasts. Microb Pathog 1999; 26: 317-323.

    Google Scholar 

  7. Menzies BE, Kourteva I. Internalization of Staphylococcus aureus by endothelial cells induces apoptosis. Infect Immun 1998; 66: 5994-5998.

    Google Scholar 

  8. Bayles KW, Wesson CA, Liou LE, et al. Intracellular Staphylococcus aureus escapes the endosome and induces apoptosis in epithelial cells. Infect Immun 1998; 66: 336-342.

    Google Scholar 

  9. Kahl BC, Goulian M, van Wamel W, et al. Staphylococcus aureus RN6390 replicates and induces apoptosis in a pulmonary epithelial cell line. Infect Immun 2000; 68: 5385-5392.

    Google Scholar 

  10. Kerr JF, Wyllie AH, Currie AR. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239-257.

    Google Scholar 

  11. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995; 267: 1456-1462.

    Google Scholar 

  12. Takahashi A. Caspase: Executioner and undertaker of apoptosis. Int J Hematol 1999; 70: 226-232.

    Google Scholar 

  13. Kroemer G, Dallaporta B, Resche-Rigon M. The mitochondrial death/life regulator in apoptosis and necrosis. Ann Rev Physiol 1998; 60: 619-642.

    Google Scholar 

  14. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998; 281: 1309-1312.

    Google Scholar 

  15. Strasser A, O'Connor L, Dixit VM. Apoptosis signaling. Annu Rev Biochem 2000; 69: 217-245.

    Google Scholar 

  16. Basu S, Kolesnick RN. Stress signals for apoptosis: Ceramide and c-Jun kinase. Oncogene 1998; 17: 3277-3285.

    Google Scholar 

  17. Grassmé H, Jekle A, Riehle A, et al. CD95 Signaling via ceramide rich membrane rafts. J Biol Chem 2001; 276: 20589-20596.

    Google Scholar 

  18. Davies RJ. Signal transduction by the JNK group of MAP kinases. Cell 2000; 103: 239-252.

    Google Scholar 

  19. Zychlinsky A, Prevost MC, Sansonetti PJ. Shigella flexneri induces apoptosis in infected macrophages. Nature 1992; 358: 167-169.

    Google Scholar 

  20. Zychlinsky A, Kenny B, Menard R, et al. IpaB mediates macrophage apoptosis induced by Shigella flexneri. Mol Microbiol 1994; 11: 619-627.

    Google Scholar 

  21. Monack DM, Mecsas J, Ghori N, Falkow S. Yersinia signals macrophages to undergo apoptosis and YopJ is necessary for this cell death. Proc Natl Acad Sci USA 1997; 94: 10385-10390.

    Google Scholar 

  22. Ruckdeschel K, Roggenkamp A, Lafont V, et al. Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis. Infect Immun 1997; 65: 4813-4821.

    Google Scholar 

  23. Hersh D, Monack DM, Smith MR, Ghori N, et al. The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. Proc Natl Acad Sci USA 1999; 96: 2396-2401.

    Google Scholar 

  24. Crane JK, Majumdar S, Pickhardt DF. Host cell death due to enteropathogenic Escherichia coli has features of apoptosis. Infect Immun 1999; 67: 2575-2584.

    Google Scholar 

  25. Hauser AR, Engel JN. Pseudomonas aeruginosa induces type-III-secretion-mediated apoptosis of macrophages and epithelial cells. Infect Immun 1999; 67: 5530-5537.

    Google Scholar 

  26. Grassmé H, Kirschnek S, Riethmueller J, et al. Host defense to Pseudomonas aeruginosa requires CD95/CD95 ligand interactions on epithelial cells. Science 2000; 290: 527-530.

    Google Scholar 

  27. Gulbins E, Bissonette R, Mahboubi A, et al. Fas induced apoptosis is mediated by a ceramide initiated Ras signaling pathway. Immunity 1995; 2: 341-351.

    Google Scholar 

  28. Zhou Q, Snipas S, Orth K, et al. Target protease specificity of the viral serpin CrmA. Analysis of five caspases. J Biol Chem 1997; 272: 7797-7800.

    Google Scholar 

  29. Mathias S, Pena LA, Kolesnick RN. Signal transduction of stress via ceramide. Biochem J 1998; 335: 465-480.

    Google Scholar 

  30. Ip YT, Davies RJ. Signal transduction by the c-Jun N-terminal kinase (JNK)-from inflammation to development. Curr Opin Cell Biol 1998; 10: 205-219.

    Google Scholar 

  31. Freemerman AJ, Turner AJ, Birrer MJ, et al. Role of c-jun in human myeloid leukemia cell apoptosis induced by pharmacological inhibitors of protein kinase C. Mol Pharmacol 1996; 49: 788-795.

    Google Scholar 

  32. Kabelitz D, Wesselborg S. Life and death of a superantigen-reactive humanCD4+ Tcell clone: Staphylococcal enterotoxins induce death by apoptosis but simultaneously trigger a proliferative response in the presence of HLA-DR+ antigen-presenting cells. Int Immunol 1992; 4: 1381-1388.

    Google Scholar 

  33. Menzies BE, Kourteva I. Staphylococcus aureus alpha-toxin induces apoptosis in endothelial cells. FEMS Immunol Med Microbiol 2000; 29: 39-45.

    Google Scholar 

  34. Wesson CA, Deringer J, Liou LE, et al. Apoptosis induced by Staphylococcus aureus in epithelial cells utilizes a mechanism involving caspases 8 and 3. Infect Immun 2000; 68: 2998-3001.

    Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, University of Tübingen, Gmelinstrasse 5, 72076, Tübingen, Germany

    M. Esen, B. Schreiner, V. Jendrossek & F. Lang

  2. Department of Neurology, University of Heidelberg/Mannheim, Theodor Kutzer Ufer, 68135, Mannheim, Germany

    K. Fassbender

  3. Department of Immunology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN, 38105, USA

    H. Grassmé

  4. Department of Immunology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN, 38105, USA

    E. Gulbins

Authors
  1. M. Esen
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  2. B. Schreiner
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  3. V. Jendrossek
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  4. F. Lang
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  5. K. Fassbender
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  6. H. Grassmé
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  7. E. Gulbins
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Esen, M., Schreiner, B., Jendrossek, V. et al. Mechanisms of Staphylococcus aureus induced apoptosis of human endothelial cells. Apoptosis 6, 431–439 (2001). https://doi.org/10.1023/A:1012445925628

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