Caspase-1–mediated pathway promotes generation of thromboinflammatory microparticles

Mitochondrial DNA–enriched microparticles promote acute-on-chronic alcoholic neutrophilia and hepatotoxicity

“…ER stress promotes particle release after E10d + 1B feeding dependent on hepatic inflammasome component caspase-1 activation. Activation of the inflammasome has been shown to contribute to alcoholic steatohepatitis in mice after chronic alcohol feeding (32) or E10d + 1B ethanol feeding (33), and activation of inflammasome component caspase-1 promotes particle release (34). We hypothesized that ER stress promotes particle release via the activation of the inflammasome in mice fed with E10d + 1B.…”

The lipid peroxidation product 4-hydroxy-2-nonenal induces tissue factor decryption via ROS generation and the thioredoxin system

“…Recently, Rothmeier et al 18 reported that ATP-induced TF decryption and TF 1 MV release results from uncoupling of the TrxR/ Trx system. Our data are in broad agreement with the concept that the TrxR/Trx system plays an important role in TF encryption/ decryption, but the role of the TrxR/Trx system in HNE-induced TF activation appears to differ from that in ATP-induced TF activation and TF 1 MV release.…”

“…[13][14][15][16] Wang et al 17 showed that thioredoxin (Trx) knockdown caused a significant increase in cell surface TF procoagulant activity in MDA-MB-231 cells, indicating that the thioredoxin reductase (TrxR)/Trx system negatively regulates TF coagulant activity. Rothmeier et al 18 reported that adenosine triphosphate (ATP)-induced TF activation and TF 1 microvesicle (MV) release in mouse macrophages is also dependent on the TrxR/Trx system. Although the mechanism by which the TrxR/Trx system regulates cell surface TF activity is unclear, it had been suggested that PDI-mediated disulfide bond formation in TF may be responsible for TF activation.…”

“…Although the mechanism by which the TrxR/Trx system regulates cell surface TF activity is unclear, it had been suggested that PDI-mediated disulfide bond formation in TF may be responsible for TF activation. 17,18 HNE was shown to inhibit Trx either directly by forming a covalent adduct with Trx or indirectly through the inhibition of TrxR activity. 19 These observations raise the possibility that HNE-induced inhibition of TrxR/Trxdependent thiol exchange pathways may be responsible for TF activation in monocytes and macrophages.…”

Not all extracellular vesicles were created equal: clinical implications

“…Danger-associated molecular patterns (DAMPs), such as extracellular ATP, are released during tissue damage and activate the inflammasome in macrophages, amplifying inflammation. Inflammasome-induced activation of an intracellular caspase-1/calpain cysteine protease cascade facilitates the formation and release of phosphatidylserinepositive, highly procoagulant microparticles (10). Thus, galectin-3, a molecule contributing to atherothrombosis, is released from monocyte macrophages in exosomes (11).…”