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. |