Summary of diverse biological effects of Stx, SPATEs, and polyphosphate that modulate activation of complement and coagulation during STEC-HUS
| Summary of diverse biological effects of Stx, SPATEs, and polyphosphate . | |
|---|---|
| Stx | |
| Direct effects that promote complement activation | • Induces release and cell surface expression of P-selectin (receptor for C3b) |
| • Induces release of VWF (site for AP convertase assembly) | |
| • Interferes with functions of FH | |
| • Induces release of C3- and C9-bearing microparticles from platelets and monocytes | |
| Direct effects that induce endothelial damage and activation of coagulation | • Activates endothelial cells, platelets, monocytes, and neutrophils |
| • Induces release of reactive oxygen species from neutrophils | |
| • Induces expression of TF | |
| • Suppresses expression of TM and TF pathway inhibitor | |
| • Induces endothelial expression of leukocyte adhesion molecules (e.g., ICAM-1, VCAM-1) | |
| • Induces platelet-neutrophil interactions | |
| • Interferes with cleavage of ULVWF by ADAMTS13 and FH | |
| • Promotes release of TF-bearing microparticles | |
| • Induces proinflammatory cytokine (e.g., TNF, IL-8) release by endothelial cells and monocytes | |
| SPATEs | |
| Pic | • Proteolyses and inactivates C2, C3/C3b, C4/C4b |
| • Des-arginates C3a | |
| EspP | • Proteolyses and inactivates C3/C3b, C5 |
| • Inactivates coagulation factor V and α2-antiplasmin | |
| StcE | • Cleaves C1-INH and increases its neutralization of C1s and MASP |
| • Binds to host/pathogen surfaces and tethers C1-INH | |
| PolyP | • Promotes coagulation activation at several steps in cascade |
| • Destabilizes C5b,6 and interferes with MAC assembly on host and pathogen | |
| • Binds to C1-INH and increases its neutralization of C1s and MASP | |
| • Binds to FH (function unknown) | |
| Summary of diverse biological effects of Stx, SPATEs, and polyphosphate . | |
|---|---|
| Stx | |
| Direct effects that promote complement activation | • Induces release and cell surface expression of P-selectin (receptor for C3b) |
| • Induces release of VWF (site for AP convertase assembly) | |
| • Interferes with functions of FH | |
| • Induces release of C3- and C9-bearing microparticles from platelets and monocytes | |
| Direct effects that induce endothelial damage and activation of coagulation | • Activates endothelial cells, platelets, monocytes, and neutrophils |
| • Induces release of reactive oxygen species from neutrophils | |
| • Induces expression of TF | |
| • Suppresses expression of TM and TF pathway inhibitor | |
| • Induces endothelial expression of leukocyte adhesion molecules (e.g., ICAM-1, VCAM-1) | |
| • Induces platelet-neutrophil interactions | |
| • Interferes with cleavage of ULVWF by ADAMTS13 and FH | |
| • Promotes release of TF-bearing microparticles | |
| • Induces proinflammatory cytokine (e.g., TNF, IL-8) release by endothelial cells and monocytes | |
| SPATEs | |
| Pic | • Proteolyses and inactivates C2, C3/C3b, C4/C4b |
| • Des-arginates C3a | |
| EspP | • Proteolyses and inactivates C3/C3b, C5 |
| • Inactivates coagulation factor V and α2-antiplasmin | |
| StcE | • Cleaves C1-INH and increases its neutralization of C1s and MASP |
| • Binds to host/pathogen surfaces and tethers C1-INH | |
| PolyP | • Promotes coagulation activation at several steps in cascade |
| • Destabilizes C5b,6 and interferes with MAC assembly on host and pathogen | |
| • Binds to C1-INH and increases its neutralization of C1s and MASP | |
| • Binds to FH (function unknown) | |
ICAM, intercellular adhesion molecule; IL, interleukin; TM, thrombomodulin; TNF, tumor necrosis factor; VCAM, vascular cell adhesion molecule.