Tissue factor in blood cells and endothelial cells

Østerud, Bjarne; Bjørklid, Eirik

doi:10.2741/376

Cited by 27 publications

(8 citation statements)

References 18 publications

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“… 2 , 3 Activated endothelial cells also secrete inflammatory cytokines and chemokines, such as IL-6, IL-8, MCP1 (macrophage chemoattractant protein 1), and RANTES (regulated upon activation, normal T cell expressed and presumably secreted), 4 , 5 and express procoagulant cofactor TF (tissue factor). 6 , 7 Endothelial cell expression of CAMs, cytokines, and chemokines in response to tissue injury and infection plays crucial roles in the recruitment, rolling, and extravasation of leukocytes at the injury site. 8 These events, along with the expression of TF, lead to thrombotic disorders, particularly venous thromboembolism.…”

mentioning

confidence: 99%

Gab2 (Grb2-Associated Binder2) Plays a Crucial Role in Inflammatory Signaling and Endothelial Dysfunction

Kondreddy

Magisetty

Keshava

et al. 2021

ATVB

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Objective: In response to inflammatory insult, endothelial cells express cell adhesion molecules and TF (tissue factor), leading to increased adhesion of leukocytes to the endothelium and activation of coagulation. Enhanced coagulation could further exacerbate inflammation. Identifying key signaling molecule(s) that drive both inflammation and coagulation may help devise effective therapeutic strategies to treat inflammatory and thrombotic disorders. The aim of the current study to determine the role of Gab2 (Grb2-associated binder2), which is known to play a crucial role in the signaling evoked by growth factors and antigen receptors, in inflammatory signaling pathways and contributing to vascular dysfunction. Approach and Results: WT (wild type) and Gab2-silenced endothelial cells were treated with TNFα (tumor necrosis factor alpha), IL (interleukin)-1β, or lipopolysaccharide (LPS). Activation of key signaling proteins in the inflammatory signaling pathways and expression of cell adhesion molecules, TF, and inflammatory cytokines were analyzed. Gab2 −/ − and WT littermate mice were challenged with LPS or S pneumoniae , and parameters of inflammation and activation of coagulation were assessed. Gab2 silencing in endothelial cells markedly attenuated TNFα-induced, IL-1β–induced, and LPS-induced expression of TF, cell adhesion molecules, and inflammatory cytokines/chemokines. Gab2 silencing suppressed TNFα-induced, IL-1β–induced, and LPS-induced phosphorylation and ubiquitination of TAK1 and activation of MAPKs (mitogen-activated protein kinases) and NF-κB (nuclear factor kappa B). Immunoprecipitation studies revealed that the Src kinase Fyn phosphorylates Gab2. Gab2 −/− mice are protected from LPS or S pneumoniae –induced vascular permeability, neutrophil infiltration, thrombin generation, NET formation, cytokine production, and lung injury. Conclusions: Our studies identify, for the first time, that Gab2 integrates signaling from multiple inflammatory receptors and regulates vascular inflammation and thrombosis.

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confidence: 99%

Gab2 (Grb2-Associated Binder2) Plays a Crucial Role in Inflammatory Signaling and Endothelial Dysfunction

Kondreddy

Magisetty

Keshava

et al. 2021

ATVB

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“…11 Tissue factor (TF) is a transmembrane receptor that binds plasma factor VII/VIIa and triggers blood coagulation after vascular injury and in various diseases. [12][13][14][15][16][17] TF is expressed by many cancer cells, particularly in cancers of epithelial origin. [18][19][20] Cancer cells also spontaneously release small membrane microparticles (MPs) bearing TF.…”

Section: Introductionmentioning

confidence: 99%

Tumor-derived tissue factor–positive microparticles and venous thrombosis in cancer patients

Geddings

Mackman

2013

Blood

284

238

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Patients with cancer have an increased risk for venous thrombosis. Interestingly, different cancer types have different rates of thrombosis, with pancreatic cancer having one of the highest rates. However, the mechanisms responsible for the increase in venous thrombosis in patients with cancer are not understood. Tissue factor (TF) is a transmembrane receptor and primary initiator of blood coagulation. Tumor cells express TF and spontaneously release TF-positive microparticles (MPs) into the blood. MPs are small membrane vesicles that are highly procoagulant. It has been proposed that these circulating tumor-derived, TF-positive MPs may explain the increased rates of venous thrombosis seen in patients with cancer. In animal models, increased levels of tumor-derived, TF-positive MPs are associated with activation of coagulation. Moreover, these MPs bind to sites of vascular injury and enhance thrombosis. We and others have found that patients with cancer have elevated levels of circulating TF-positive MPs. These MPs are derived from tumors because they express tumor markers and are decreased by tumor resection. Importantly, several studies have shown that increased levels of TF-positive MPs correlate with venous thrombosis in patients with cancer. Taken together, these results suggest that TF-positive MPs may be a useful biomarker to identify patients with cancer who are at high risk for thrombosis.

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“…EC are well documented to synthesize TF by several agonists such as thrombin, lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α in vitro. 23 A recent report by Pawlinski and Mackman, however, failed to show that TF on the endothelium may play any role in thrombin generation in a murine endotoxemia model. 24 In contrast to EC, SMC constitutively express TF in vitro and in vivo, providing the vessel with a hemostatic barrier.…”

Section: Discussionmentioning

confidence: 99%

Effect of Smoking Status on Monocyte Tissue Factor Activity, Carotid Atherosclerosis and Long-Term Prognosis in Metabolic Syndrome

Kohashi

Nakagomi

Morisawa

et al. 2018

Circ J

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Tissue factor in blood cells and endothelial cells

Cited by 27 publications

References 18 publications

Gab2 (Grb2-Associated Binder2) Plays a Crucial Role in Inflammatory Signaling and Endothelial Dysfunction

Gab2 (Grb2-Associated Binder2) Plays a Crucial Role in Inflammatory Signaling and Endothelial Dysfunction

Tumor-derived tissue factor–positive microparticles and venous thrombosis in cancer patients

Effect of Smoking Status on Monocyte Tissue Factor Activity, Carotid Atherosclerosis and Long-Term Prognosis in Metabolic Syndrome

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