Summary
Tissue factor (TF), the cellular receptor and cofactor for factor VII/VIIa, initiates
haemostasis and thrombosis. Initial tissue distribution studies suggested that TF
was sequestered from the circulation and only present at perivascular sites. However,
there is now clear evidence that TF also exists as a blood-borne form with critical
contributions not only to arterial thrombosis following plaque rupture and to venous
thrombosis following endothelial perturbation, but also to various other clotting
abnormalities associated with trauma, infection, or cancer. Because thrombin generation,
fibrin deposition, and platelet aggregation in the contexts of haemostasis, thrombosis,
and pathogen defence frequently occur without TF de novo synthesis, considerable efforts are still directed to understanding the molecular
events underlying the conversion of predominantly non-coagulant or cryptic TF on the
surface of haematopoietic cells to a highly procoagulant molecule following cellular
injury or stimulation. This article will review some of the still controversial mechanisms
implicated in cellular TF activation or decryption with particular focus on the coordinated
effects of outer leaflet phosphatidylserine exposure and thiol-disulfide exchange
pathways involving protein disulfide isomerase (PDI). In this regard, our recent findings
of ATP-triggered stimulation of the purinergic P2X7 receptor on myeloid and smooth
muscle cells resulting in potent TF activation and shedding of procoagulant microparticles
as well as of rapid monocyte TF decryption following antithymocyte globulin-dependent
membrane complement fixation have delineated specific PDIdependent pathways of cellular
TF activation and thus illustrated additional and novel links in the coupling of inflammation
and coagulation.
Keywords Tissue factor - phosphatidylserine - protein disulfide isomerase - thioldisulfide
exchange - thrombosis
