Stored platelets contain residual amounts of tissue factor: evidence from studies on platelet concentrates stored for prolonged periods

Pérez-Pujol, Sı́lvia; Aras, Ömer; Lozano, Miguel; Cocking-Johnson, Debra; Key, Nigel S.; White, James G.; McCullough, J. Mac; Escolar, Ginés

doi:10.1111/j.0041-1132.2005.04224.x

Cited by 15 publications

(13 citation statements)

References 42 publications

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“…While some authors neither detected TF antigen nor activity in resting as well as calcium ionophore-or collagen-stimulated platelets, 52 others described functional TF in platelets. [53][54][55][56][57] Indeed, different mechanisms of TF expression in platelets have been described, underscoring a potential role of platelet TF. Translocation and activation of existing TF protein from intracellular compartments to the platelet surface, uptake of TF from other sources, mainly via MPs, and de novo TF mRNA and protein synthesis have been proposed (Figure 4).…”

Section: Granulocytesmentioning

confidence: 99%

Tissue Factor and Cardiovascular Disease: Quo Vadis?

Berndt

Tanner

Lüscher

2010

Circ J

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The coagulation cascade represents a system of proteases responsible to maintain vascular integrity and to induce rapid clot formation after vessel injury. Tissue factor (TF), the key initiator of the coagulation cascade, binds to factor VIIa and thereby activates factor IX and factor X, resulting in thrombus formation. Different stimuli enhance TF gene expression in endothelial and vascular smooth muscle cells. In addition to these vascular cells, TF has recently been detected in the bloodstream in circulating cells such as leukocytes and platelets, as a component of microparticles, and as a soluble, alternatively spliced form of TF. Various cardiovascular risk factors like hypertension, diabetes, and dyslipidemia, increase levels of TF. In line with this observation, enhanced vascular TF expression occurs during atherogenesis, particularly in patients with acute coronary syndromes. (Circ J 2010; 74: 3 - 12)

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Section: Granulocytesmentioning

confidence: 99%

Tissue Factor and Cardiovascular Disease: Quo Vadis?

Berndt

Tanner

Lüscher

2010

Circ J

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“…Nevertheless, TF-containing platelets have been identified by several investigators [63,[70][71][72][73]. In resting platelets, TF is found at the membrane and in the matrix of α-granules as well as in the open canalicular system [63], whereas stimulation with different agonists leads to the presentation of TF on the platelet surface [63].…”

Section: Plateletsmentioning

confidence: 99%

Tissue factor: beyond coagulation in the cardiovascular system

2009

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TF (tissue factor) is the main trigger of the coagulation cascade; by binding Factor VIIa it activates Factor IX and Factor X, thereby resulting in fibrin formation. Various stimuli, such as cytokines, growth factors and biogenic amines, induce TF expression and activity in vascular cells. Downstream targets of these mediators include diverse signalling molecules such as MAPKs (mitogen-activated protein kinases), PI3K (phosphoinositide 3-kinase) and PKC (protein kinase C). In addition, TF can be detected in the bloodstream, known as circulating or blood-borne TF. Many cardiovascular risk factors, such as hypertension, diabetes, dyslipidaemia and smoking, are associated with increased expression of TF. Furthermore, in patients presenting with acute coronary syndromes, elevated levels of circulating TF are found. Apart from its role in thrombosis, TF has pro-atherogenic properties, as it is involved in neointima formation by inducing vascular smooth muscle cell migration. As inhibition of TF action appears to be an attractive target for the treatment of cardiovascular disease, therapeutic strategies are under investigation to specifically interfere with the action of TF or, alternatively, promote the effects of TFPI (TF pathway inhibitor).

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“…It has been proposed that platelets can carry variable amounts of TF under different experimental and clinical situations [Zillmann et al, 2001;Balasubramanian et al, 2002;Muller et al, 2003;del Conde et al, 2005;Perez-Pujol et al, 2005]. Whether platelet related TF is constitutionally present in platelets or transferred from other cells is subject of controversy, though the second possibility seems the more plausible [Camera et al, 2012].…”

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confidence: 99%

Internalization of Tissue Factor-Rich Microvesicles by Platelets Occurs Independently of GPIIb-IIIa, and Involves CD36 Receptor, Serotonin Transporter and Cytoskeletal Assembly

et al. 2015

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Platelets are important in hemostasis, but also detect particles and pathogens in the circulation. Phagocytic and endocytic activities of platelets are widely recognized; however, receptors and mechanisms involved remain poorly understood. We previously demonstrated that platelets internalize and store phospholipid microvesicles enriched in human tissue factor (TF+MVs) and that platelet-associated TF enhances thrombus formation at sites of vascular damage. Here, we investigate the mechanisms implied in the interactions of TF+MVs with platelets and the effects of specific inhibitory strategies. Aggregometry and electron microscopy were used to assess platelet activation and TF+MVs uptake. Cytoskeletal assembly and activation of phosphoinositide 3-kinase (PI3K) and RhoA were analyzed by western blot and ELISA. Exposure of platelets to TF+MVs caused reversible platelet aggregation, actin polymerization and association of contractile proteins to the cytoskeleton being maximal at 1 min. The same kinetics were observed for activation of PI3K and translocation of RhoA to the cytoskeleton. Inhibitory strategies to block glycoprotein IIb-IIIa (GPIIb-IIIa), scavenger receptor CD36, serotonin transporter (SERT) and PI3K, fully prevented platelet aggregation by TF+MVs. Ultrastructural techniques revealed that uptake of TF+MVs was efficiently prevented by anti-CD36 and SERT inhibitor, but only moderately interfered by GPIIb-IIIa blockade. We conclude that internalization of TF+MVs by platelets occurs independently of receptors related to their main hemostatic function (GPIIb-IIIa), involves the scavenger receptor CD36, SERT and engages PI3-Kinase activation and cytoskeletal assembly. CD36 and SERT appear as potential therapeutic targets to interfere with the association of TF+MVs with platelets and possibly downregulate their prothrombotic phenotype.

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Stored platelets contain residual amounts of tissue factor: evidence from studies on platelet concentrates stored for prolonged periods

Cited by 15 publications

References 42 publications

Tissue Factor and Cardiovascular Disease: Quo Vadis?

Tissue Factor and Cardiovascular Disease: Quo Vadis?

Tissue factor: beyond coagulation in the cardiovascular system

Internalization of Tissue Factor-Rich Microvesicles by Platelets Occurs Independently of GPIIb-IIIa, and Involves CD36 Receptor, Serotonin Transporter and Cytoskeletal Assembly

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