Table 1

Selected in vitro studies implicating lethal (LT) or edema toxin (ET) in endothelial cell dysfunction
Study Toxin Cell type Toxin effect
Rolando, M. 2010 LT HUVEC Exerted cytotoxic effects on endothelial cell monolayers with elongation and redistribution of VE-cadherin and subsequent cell death; increased caspase-3, 8 and 9 activity. Up-regulation of TNF-related apoptosis-inducing ligand (TRAIL) and down-regulation of xaf1 (XIAP associated factor-1) participated in LT-induced caspase-3 activation; increased caspase-3 dependent cortactin and rhophilin-2 activity in combination with calponin-1 expression appeared necessary for LT mediated actin cable formation.
Guichard, A. 2010 LT Human brain, dermal and lung microvascular endothelial cells (HBMEC, HDMEC and HMVEC-Ls, respectively) Lethal factor (LF) worked synergistically with edema factor (EF) to reduce DE-cadherin levels at adherens junctions in HBMEC, HDMECs and HMVEC-Ls.
Warfel, J. 2011 LT Human lung microvascular endothelial cells Increased monolayer permeability, effects on permeability associated with the activation of Rho associated kinase (ROCK-1) and increased myosin light chain (MLC) phosphorylation and subsequent actin stress fiber formation and VE-cadherin gene and protein expression inhibition.
Liu, T. 2012 LT Rat pulmonary microvascular endothelial cells Increased gap formation and permeability of endothelial cell monolayers; decreased p38 signaling; permeability effects overcome by pmHSP27 over-expression.
Guichard, A. 2010 ET Human brain, dermal and lung microvascular endothelial cells (HBMEC, HDMEC and HMVEC-Ls, respectively) Edema factor (EF) worked synergistically with lethal factor (LF) to reduce DE-cadherin levels at adherens junctions in HBMEC, HDMECs and HMVEC-Ls.
EF increased the permeability of HBMEC trans-well monolayers.
Maddugoda, M. 2011 ET Mouse endothelial cells, HUVEC Stimulated trans-endothelial macro-aperture (TEM) tunnel formation and increased endothelial permeability potentially via cAMP mediated mechanisms.
Ebrahimi, C. 2011 ET HBMEC Disrupted tight junction formation and barrier function and monolayer integrity; contributed to disruption of endothelial cells and ZO-1, a primary regulatory protein of tight junction formation in the blood?brain barrier.

Remy et al.

Remy et al. BMC Medicine 2013 11:217   doi:10.1186/1741-7015-11-217

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