Tissue Factor encryption and decryption: Facts and controversies

Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, USA.
Thrombosis Research (Impact Factor: 2.43). 03/2012; 129 Suppl 2:S13-7. DOI: 10.1016/j.thromres.2012.02.021
Source: PubMed

ABSTRACT Tissue factor (TF)-initiated coagulation plays a critical role in both hemostasis and thrombosis. It is generally believed that most of the tissue factor expressed on cell surfaces is maintained in a cryptic, i.e., coagulantly inactive state and an activation step (decryption) is required for the expression of maximum TF procoagulant activity. However, what exactly constitutes cryptic or procoagulant TF, molecular differences between these two forms and mechanisms that are responsible for transformation from one to the other form are not entirely clear and remain highly controversial, thus are a matter of ongoing debate. This brief review discusses pertinent literature on TF encryption/decryption with specific emphasis on the role of membrane phospholipids and reduction/oxidation of the TF Cys186-Cys209 disulfide bond in regulating TF activity at cell surfaces.

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Available from: Hema Kothari, Jul 19, 2015
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    • "This complex is able to activate FX, which in turn results in thrombin, which is responsible for thrombus stabilization (Monroe et al., 2002). Moreover, membrane-embedded TF is usually in inactive coagulant state (cryptic) while it requires activation to reach its full potency (decryption) (Rao et al., 2012). However, the mechanism behind the activation of circulating TF is not yet elucidated and such information would provide a significant breakthrough in the understanding of in vivo thrombosis. "
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    ABSTRACT: The production of TF by neutrophils and their contribution in thrombosis was until recently a matter of scientific debate. Experimental data suggested the de novo TF production by neutrophils under inflammatory stimuli, while others proposed that these cells acquired microparticle-derived TF. Recent experimental evidence revealed the critical role of neutrophils in thrombotic events. Neutrophil derived TF has been implicated in this process in several human and animal models. Additionally, neutrophil extracellular trap (NET) release has emerged as a major contributor in neutrophil-driven thrombogenicity in disease models including sepsis, deep venous thrombosis, and malignancy. It is suggested that NETs provide the scaffold for fibrin deposition and platelet entrapment and subsequent activation. The recently reported autophagy-dependent extracellular delivery of TF in NETs further supports the involvement of neutrophils in thrombosis. Herein, we seek to review novel data regarding the role of neutrophils in thrombosis, emphasizing the implication of TF and NETs.
    Frontiers in Immunology 12/2012; 3:385. DOI:10.3389/fimmu.2012.00385
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    ABSTRACT: Tissue factor (TF) is the high affinity receptor for factor VII (FVII)/VIIa [1]. It is expressed by cells surrounding blood vessels and in certain tissues and is required for hemostasis [2]. During Gram-negative bacterial infection, lipopolysaccharide (LPS) induces TF expression in circulating monocytes [3-5] resulting in local clot formation to immobilize the bacterium and limit the spread of the infection. © 2012 International Society on Thrombosis and Haemostasis.
    Journal of Thrombosis and Haemostasis 07/2012; 10(9):1965-7. DOI:10.1111/j.1538-7836.2012.04842.x · 5.55 Impact Factor
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    ABSTRACT: Intimate links connect tissue factor (TF), the principal initiator of the clotting cascade, to inflammation, a cross-talk amplified by locally generated Angiotensin (ANG) II, the effector arm of the Renin Angiotensin System (RAS). The RAS, in turn, plays a pathophysiological role in diabetes, a proinflammatory state to which elevated glucose, the disease hallmark, contributes by activating key signalling pathways and increasing the cellular content of RAS components. To evaluate the effect of high glucose concentrations on TF antigen (Ag) expression and procoagulant activity (PCA) in lipopolysaccharide(LPS)-primed human mononuclear cell(MNC)s and to test whether pharmacological RAS blockade modifies that pattern. LPS-activated MNCs exposed to increasing D-glucose (from 5.5 to 50mM) in absence or presence of aliskiren, a renin inhibitor, zofenopril, an ANG converting enzyme inhibitor, and olmesartan, an ANGII type I receptor blocker. PCA was assessed by one-stage clotting assay and TF antigen expression by ELISA. Increasing ambient glucose (range 5.5-50mM) potentiated LPS-induced PCA and TF Ag expression. Aliskiren, zofenopril and olmesartan downregulated those responses but the efficacy of the former decreased by ascending drug concentration while both zofenopril and olmesartan showed an opposite behaviour. TF Ag expression modulation by RAS blockade was stronger in 50 than 5mM ambient glucose. High glucose potentiates the procoagulant action of LPS in human MNCs and RAS blockers downregulate that response possibly as a reflection of the underlying involvement of the system in that mechanism.
    Thrombosis Research 07/2012; 130(3):552-6. DOI:10.1016/j.thromres.2012.06.022 · 2.43 Impact Factor
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