Tissue factor expression in blood cells

doi:10.1016/j.thromres.2010.01.032

Thrombosis Research

Volume 125, Supplement 1, April 2010, Pages S31-S34

https://doi.org/10.1016/j.thromres.2010.01.032 Get rights and content

Abstract

The popular concept of TF serving predominantly as a hemostatic envelope encapsulating the vascular bed, has recently been challenged by the observation that blood of healthy individuals may form TF-induced thrombus under conditions entailing shear stress and activated platelets, corroborating the notion of blood borne TF. Accordingly, small amounts of TF activity is detected in calcium ionophore-stimulated monocytes, whereas it is questionable whether neutrophils and eosinophils express TF. Still there are contradicting reports on TF synthesis and expression in activated platelets, but when using a very sensitive and specific assay for TF activity measurements, we fail to detect TF activity associated with platelets activated with various agonists. However, activated platelets may play a role in decrypting monocyte TF activity in a process entailing transfer of TF to activated platelets in a P-seelctin –PSGL-1 reaction whereby inactive TF (encrypted) becomes active through the availability of clusters of phosphatidylserine. Microparticles from plasma of healthy subjects possess weak TF-like activity which is not inactivated by anti-TF antibody. Endothelial cells are well documented to synthesize TF by several agonists in vitro. In contrast, there is little evidence that these cells are capable of synthesizing TF in vivo, and a recent report fails to show that TF on the endothelium may play any role in thrombin generation in a murine endotoxemia model. It may be concluded that monocytes are the only blood cells that synthesize and express TF and which may be the only source for TF-induced thrombosis when the endothelium is intact.

Section snippets

Tissue factor (TF) in monocytes

The classical concept of TF distribution has until quite recently been that TF is entirely localized in the extravascular system, i.e. the vessel wall prevents blood from contact with TF. Within the human blood, monocytes have been recognized as the only cell type that can be induced to synthesize TF de novo. Recently this has been challenged, first by the reports of TF associated with the neutrophils, and then by the reports of the presence of TF in platelets. Furthermore, circulating

Lack of tissue factor in granulocytes

In contrast to the reports of TF activity expression in human neutrophils and eosinophils [7], [8], [9], [10], we showed that human granulocytes, isolated from stimulated whole blood, contain very low levels of TF activity, whereas plated resting or LPS/PMA-stimulated granulocytes did not possess any TF activity or antigen [11]. This may suggest that granulocytes acquire TF but do not synthesize it themselves. Our data demonstrated that in experiments, when whole blood was reconstituted with

TF in microparticles

There have also been conflicting reports on TF associated with microparticles. Obviously TF-rich microparticles may be found in the circulation of patients with various diseases, e.g. severe septicaemia, unstable angina, etc [for review see 13) whereas the presence of TF associated with microparticles in the blood of healthy individuals may be questioned. We found that the TF activity of microparticles from non-stimulated blood was not detecable [4], [14]. Although microparticles from

TF expression in platelets?

The association of TF with platelets was first suggested in a study in which platelets were required for the rapid appearance of TF belonging to the blood, and platelet conjugates were identified as major sites of TF presentation in the blood [19]. An extension of this study revealed TF stored within α-granula and the open canalicular system of the platelets [20]. Following activation with either collagen or thrombin, TF activity was exposed on the platelet membrane. Recently, other reports

TF expression in endothelial cells (ECs)

A number of groups found TF in cultured human endothelial cells (HUVECs) upon perturbation [for review see 30]. It was demonstrated first that thrombin was an agonist of TF induction in HUVECs and later LPS, IL-1ß and TNFα were shown to induce TF in ECs. [for review see 31]. Until 1987 it had not been possible to identify TF localization in various tissues as generation of monospecific antibodies by using purified TF was not available. The new technique of affinity purifying TF as well as the

Conflict of interest

None.

Acknowledgement

This work was supported by grants from the Norwegian Research Council.

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Review ArticleTissue factor expression in blood cells

Abstract

Section snippets

Tissue factor (TF) in monocytes

Lack of tissue factor in granulocytes

TF in microparticles

TF expression in platelets?

TF expression in endothelial cells (ECs)

Conflict of interest

Acknowledgement

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Review Article
Tissue factor expression in blood cells