biostudies-literatureWang JNHLBI NIH HHS645-655https://www.ebi.ac.uk/biostudies/studies/S-EPMC6695563biostudies-literatureUnknown134(7)Tissue factor (TF) is a cofactor for factor VIIa and the primary cellular initiator of coagulation. Typically, most TF on cell surfaces exists in a cryptic coagulant-inactive state but are transformed to a procoagulant form (decryption) following cell activation. Our recent studies in cell model systems showed that sphingomyelin (SM) in the outer leaflet of the plasma membrane is responsible for maintaining TF in an encrypted state in resting cells, and the hydrolysis of SM leads to decryption of TF. The present study was carried out to investigate the relevance of this novel mechanism in the regulation of TF procoagulant activity in pathophysiology. As observed in cell systems, administration of adenosine triphosphate (ATP) to mice enhanced lipopolysaccharide (LPS)-induced TF procoagulantBloodAcid sphingomyelinase plays a critical role in LPS- and cytokine-induced tissue factor procoagulant activity.PMC6695563R01 HL124055Rao LVMPendurthi URWang JfalseAcid sphingomyelinase plays a critical role in LPS- and cytokine-induced tissue factor procoagulant activity.Tissue factor (TF) is a cofactor for factor VIIa and the primary cellular initiator of coagulation. Typically, most TF on cell surfaces exists in a cryptic coagulant-inactive state but are transformed to a procoagulant form (decryption) following cell activation. Our recent studies in cell model systems showed that sphingomyelin (SM) in the outer leaflet of the plasma membrane is responsible for maintaining TF in an encrypted state in resting cells, and the hydrolysis of SM leads to decryption of TF. The present study was carried out to investigate the relevance of this novel mechanism in the regulation of TF procoagulant activity in pathophysiology. As observed in cell systems, administration of adenosine triphosphate (ATP) to mice enhanced lipopolysaccharide (LPS)-induced TF procoagulant2019-01-01T00:00:00Z2019 Aug2025-04-06T23:12:51.123Z2025-04-04T09:42:42.93ZS-EPMC66955633126278210.1182/blood.2019001400