Differential cytotoxic actions of Shiga toxin 1 and Shiga toxin 2 on microvascular and macrovascular endothelial cells

Andreas Bauwens, Martina Bielaszewska, Björn Kemper, Patrik Langehanenberg, Gert Von Bally, Rudolf Reichelt, Dennis Mulac, Hans Ulrich Humpf, Alexander W. Friedrich, Kwang S. Kim, Helge Karch, Johannes Müthing

Research output: Contribution to journalArticle

Abstract

Shiga toxin (Stx)-mediated injury to vascular endothelial cells in the kidneys, brain and other organs underlies the pathogenesis of haemolytic uraemic syndrome (HUS) caused by enterohaemorrhagic Escherichia coli (EHEC). We present a direct and comprehensive comparison of cellular injury induced by the two major Stx types, Stx1 and Stx2, in human brain microvascular endothelial cells (HBMECs) and EA.hy 926 macrovascular endothelial cells. Scanning electron microscopy of micro-carrier-based cell cultures, digital holographic microscopy of living single cells, and quantitative apoptosis/necrosis assays demonstrate that Stx1 causes both necrosis and apoptosis, whereas Stx2 induces almost exclusively apoptosis in both cell lines. Moreover, microvascular and macrovascular endothelial cells have different susceptibilities to the toxins: EA.hy 926 cells are slightly, but significantly (∼ 10 times) more susceptible to Stx1, whereas HBMECs are strikingly (≥ 1,000 times) more susceptible to Stx2. These findings have implications in the pathogenesis of HUS, and suggest the existence of yet to be delineated Stx type-specific mechanisms of endothelial cell injury beyond inhibition of protein biosynthesis.

Original languageEnglish (US)
Pages (from-to)515-528
Number of pages14
JournalThrombosis and Haemostasis
Volume105
Issue number3
DOIs
StatePublished - Mar 1 2011

Keywords

  • Apoptosis
  • Endothelial cells
  • Enterohaemorrhagic e. Coli
  • Necrosis
  • Shiga toxin
  • Single cell analysis

ASJC Scopus subject areas

  • Hematology

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  • Cite this

    Bauwens, A., Bielaszewska, M., Kemper, B., Langehanenberg, P., Von Bally, G., Reichelt, R., Mulac, D., Humpf, H. U., Friedrich, A. W., Kim, K. S., Karch, H., & Müthing, J. (2011). Differential cytotoxic actions of Shiga toxin 1 and Shiga toxin 2 on microvascular and macrovascular endothelial cells. Thrombosis and Haemostasis, 105(3), 515-528. https://doi.org/10.1160/TH10-02-0140