Tissue factor expression in blood cells.
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-selectin-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.
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Tissue factor (TF) is the primary activator of coagulation and is mainly produced by monocytes in an inflammatory state.
“Tissue factor (TF) is the primary activator of coagulation and is mainly produced by monocytes in an inflammatory state (Østerud, 2010).”
From The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1 (2021) · cites this paper as Østerud, 2010
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BackgroundResultTissue factor–positive neutrophils bind to injured endothelial wall and initiate thrombus formation
Darbousset, R., Thomas, G. M., Mezouar, S., Frère, C., Bonier, R., Mackman, N., Renné, T., Dignat‐George, F., Dubois, C., & Panicot‐Dubois, L. (2012) · Blood · doi:10.1182/blood-2012-06-437772 · Cited by 323 · see citing works
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“TF is a key player in the activation of the coagulation pathway, yet its action is determined not only by its expression levels, but also by its accessibility in terms of conformational state that is controversial for different cells types or conditions (128).”
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“TF is expressed by the injured blood vessel wall (adventitial fibroblasts, smooth muscle cells and pericytes), platelets, activated endothelium, macrophages, neutrophils, circulating microparticles, and epithelial cells (105, 106).”
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“Previous studies have shown that monocytes are the principal source of tissue factor in healthy participants.(41) However, platelet surface tissue factor and P-selectin were found to be higher in patients with PV or ET compared with controls and increased with JAK2 allelic burden.”
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“Tissue factor (TF) is the primary activator of coagulation and is mainly produced by monocytes in an inflammatory state (Østerud, 2010).”
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“While monocytes are the only blood cells convincingly demonstrated to synthesize and express TF, its presence in other blood cells such as platelets and circulating MPs has been disputed [5,6].”
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“Furthermore, platelets and neutrophils are important sources of TF and are known to secrete TF in response to thrombin (23).”
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“Investigators who did not detect TF activity in platelets strongly believe that the only blood cells capable of synthesizing TF are the monocytes which may be the only source for TF-induced thrombosis when the endothelium is intact [39-41].”
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“Presence of TF mRNA has been demonstrated in monocytes (Osterud, 2010) endothelial cells (Bavendiek et al.”
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“Although TF expression in these blood cells is a matter of debate, monocytes are probably the only blood cells that synthesize and express TF [53].”
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“In response to this, activated monocytes and endothelial cells, as well as their microparticles, express and release activated TF at pathogen exposure sites (30, 31).”
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“A possible contribution from platelets was not investigated, however, according to Osterud and his investigation of blood derived TF sources, platelets are not synthesizing TF [31].”
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“The activated monocytes synthesize and express almost all of the tissue factor (TF) in the blood cells (8, 9), which manifests not only as a hypercoagulable but also as an inflammatory state (10).”
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“endothelial and vascular smooth muscle cells, platelets, leukocytes, monocytes, fibroblasts, keratinocytes) as well as in plasma, but at very low levels (blood-borne TF) [1].”
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“A prominent risk resulting in vascular injury is exposure of blood to an extravascular tissue factor and activation of the coagulation cascade that may lead to vascular clot formation (33,34), BBB dysfunction and blood flow impairment (35).”
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“For instance, TF can be found on circulating monocytes [4], on extracellular vesicles (EVs) [5], and as a soluble, alternatively spliced form that has low procoagulant activity [6].”
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“TF mRNA levels are increased after stimulation (26).”
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“Tissue factor is present in monocytes and surface expressed following activation of these inflammatory cells by cytokines [23].”
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“TF is then transferred from monocytes to platelets (7, 21).”
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“The cellular source of TF in blood is still a matter of discussion, but it has been concluded that monocytes are the only blood cells that synthesize and express TF [4].”
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“It is well established that protective neutrophil effector functions during infection can be accompanied by severe collateral damage due to their tissue damaging properties by releasing inflammatory mediators such as IL1β (Liu and Sun, 2019) and reactive oxygen species (Kolaczkowska and Kubes, 2013) or via tissuefacto…”
BackgroundTissue Factor-Dependent Chemokine Production Aggravates Experimental Colitis
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p38/TF/HIF-α Signaling Pathway Participates in the Progression of CIPN in Mice
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“reactive protein could upregulate TF expression in circulating monocytes and extravasated macrophages [35–37].”
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“It is possible that most TF is inactive, and that the decryption of TF is dependent upon exposed PS [34].”
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“There is no porcine assay currently available to measure TF, and there are disagreements between studies regarding whether circulating TF is physiologically active [33,34].”
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“In humans as well as mice, TF is expressed in many tissues and cell types including monocytic and vascular smooth muscle cells; the reader is advised to consult a stellar review that thoroughly covers this subject (23), but it is pertinent to note that the role and/or (patho)physiological significance of constitutive…”
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“Mezzano and Panes also revealed that von Willebrand Factor (vWF) plus Ristocetin might induce TF activity in platelets in short time and that cell membranes needed to be intact (not lysed) in order to detect TF activity (19, 21).”
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“Although there is much on debate on the TF expression in blood cells, it is likely that monocytes are the only blood cells that synthesize and express TF (Østerud, 2010).”
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“Although TF expression by blood cells remains controversial, monocytes are the only blood cells that are known to synthesize and express TF [31].”
BackgroundDOCTEUR DE L'UNIVERSITE DE REIMS CHAMPAGNE - ARDENNE Discipline : Biologie Cellulaire et Moléculaire
Doctorale, É., & Sante, T. E. (2014)
- Authors
- Østerud, B.
- Affiliations
- UiT The Arctic University of Norway (NO)
- Corresponding author
- Østerud, Bjarne
- ORCID
- Østerud, Bjarne
- Venue
- Thrombosis Research
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 125
- Pages
- S31-S34
- ISSN
- 0049-3848 (ISSN-L)
- OpenAlex
- W2044057465
- Cited by
- 111
- References
- 31
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 9 · 2014: 11 · 2013: 15 · 2012: 20
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thrombosis Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
- Keywords
- tissue factor, blood cells, monocytes, platelets, neutrophils, eosinophils, endothelial cells, shear stress, P-selectin, PSGL-1, phosphatidylserine, microparticles, thrombin generation, endotoxemia, hemostasis
- MeSH terms
- Animals, Blood Platelets, Eosinophils, Humans, Monocytes, Neutrophils, Phosphatidylserines, Thrombin, Thromboplastin, Thrombosis, Platelet Activation, P-Selectin, Endotoxemia, Endothelial Cells, Mice
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