The role of monocytes in thrombotic disorders

2009 ◽  
Vol 102 (11) ◽  
pp. 916-924 ◽  
Author(s):  
Gregory Lip ◽  
Eduard Shantsila
Keyword(s):  
Innate Immunity ◽  
Dendritic Cells ◽  
Tissue Factor ◽  
Physiological Role ◽  
Coagulation Cascade ◽  
Pathophysiological Role ◽  
Platelet Aggregates

SummaryAlthough, the main physiological role of monocytes is attributed to innate immunity (that is, phagocytosis) and the development of tissue macrophages and dendritic cells, the pathophysiological role of these goes far behind these (simplistic) limits. Indeed, monocytes constitute a major source of blood tissue factor, a key element of the extrinsic coagulation cascade. Monocytes actively bind to platelets, thus forming very prothrombotic monocyte-platelet aggregates. Additionally, these cells link inflammation and the procoagulant state observed in various prothrombotic conditions. However, monocytes are also crucial for successful thrombus recanalisation. In this article, we review the available data on potential mechanisms that link monocytes with thrombosis-related processes.

CD209 (DC-SIGN) – role in the work of the innate immunity and pathogen penetration

2020 ◽  
Vol 1 (9) ◽  
pp. 64-71
Author(s):  
E. A. Klimov ◽  
◽  
E. K. Novitskaya ◽  
S. N. Koval’chuk ◽  
◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Dendritic Cells ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Adhesion Molecule ◽  
Immune Evasion ◽  
Intercellular Adhesion Molecule ◽  
Lectin Receptor

Intercellular adhesion molecule CD209 (DC-SIGN) is a membrane C-type lectin receptor expressed on the surface of dendritic cells and macrophages. CD209 plays an important role in innate immunity. Many studies have shown the possibility of interaction of the CD209 molecule with a number of dangerous pathogens of humans and animals. This review summarizes information on the structure of the CD209 gene and its product, describes the role of the CD209 protein in the immune response, in the migration of dendritic cells from the blood to the tissue, and their interaction with neutrophils. The currently known signaling pathway of activation through the CD209 inflammatory response is presented. The role of CD209 as an endocytic antigen receptor and the participation of the protein in immune evasion of pathogens are discussed. The mechanisms known to date for the development of infections caused by pathogens of various nature in animals are described.

The role of factor XIII-A in the development of inflammatory skin lesions

2014 ◽  
Vol 9 (9) ◽  
pp. 869-873 ◽  
Author(s):  
Marcin Włodarczyk ◽  
Aleksandra Sobolewska ◽  
Aleksandra Lesiak ◽  
Joanna Narbutt
Keyword(s):  
Dendritic Cells ◽  
Factor Xiii ◽  
Skin Lesions ◽  
Coagulation Cascade ◽  
Clotting Factor ◽  
Cellular Functions ◽  
Last Stage ◽  
Inflammatory Skin ◽  
The Relationship

AbstractFactor XIII (FXIII) is a unique clotting factor activated in the last stage of the coagulation cascade, with multiple other plasmatic and cellular functions, outside of the traditional homeostasis. Literature data show that FXIII is expressed in skin lesions in the course of various inflammatory skin disorders. Dermis contains a series of macrophages and dendritic cells, which express different phenotypes including FXIII. Increased levels of FXIII-positive cells are present in specific cutaneous inflammatory and fibrotic conditions. The aim of this review is to provide the relationship between FXIII and the development of the inflammatory skin lesions.

scholarly journals Should We Replace the Terms Intrinsic and Extrinsic Coagulation Pathways With Tissue Factor Pathway?

2016 ◽  
Vol 23 (8) ◽  
pp. 922-927 ◽  
Author(s):  
Jan F. Vojacek
Keyword(s):  
Tissue Factor ◽  
Coagulation Cascade ◽  
Coagulation System ◽  
Bleeding Complications ◽  
Antithrombotic Agents ◽  
Risk Of Bleeding ◽  
Tissue Factor Pathway ◽  
The Common ◽  
Coagulation Pathway

Present review highlights some new aspects of the role of individual components of blood coagulation process and proposes a modified concept of hemocoagulation cascade. The role of FXII in the initiation of the so-called intrinsic coagulation system is currently questioned. Its role has been recently demonstrated mainly in the thrombus propagation and final stabilization together with factors XI and XIII. The edited concept underlines the common part of the tissue factor (TF) in the initiation of both the intrinsic and extrinsic pathways of the coagulation system and therefore may make it not improperly be called the TF coagulation pathway. The search for new antithrombotic agents shows that the level of the coagulation system blockade depends on which step in the coagulation cascade is targeted and results in different degrees of the antithrombotic efficiency and the risk of bleeding complications.

scholarly journals Innate Immunity toLeishmaniaInfection: Within Phagocytes

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Marcela Freitas Lopes ◽  
Ana Caroline Costa-da-Silva ◽  
George Alexandre DosReis
Keyword(s):  
Innate Immunity ◽  
Dendritic Cells ◽  
Tissue Repair ◽  
Leishmania Major ◽  
Host Cells ◽  
Infection Site ◽  
Experimental Findings ◽  
Inflammatory Macrophages

Infection byLeishmaniatakes place in the context of inflammation and tissue repair. Besides tissue resident macrophages, inflammatory macrophages and neutrophils are recruited to the infection site and serve both as host cells and as effectors against infection. Recent studies suggest additional important roles for monocytes and dendritic cells. This paper addresses recent experimental findings regarding the regulation ofLeishmania majorinfection by these major phagocyte populations. In addition, the role of IL-4 on dendritic cells and monocytes is discussed.

scholarly journals Striatonigrostriatal Spirals in Addiction

2021 ◽  
Vol 15 ◽  
Author(s):  
Andy Sivils ◽  
John Q. Wang ◽  
Xiang-Ping Chu
Keyword(s):  
Substance Use ◽  
Basal Ganglia ◽  
Positive Emotions ◽  
Physiological Role ◽  
Reward System ◽  
Pathophysiological Role ◽  
The Us ◽  
Goal Directed Behavior ◽  
Economic Choices

A biological reward system is integral to all animal life and humans are no exception. For millennia individuals have investigated this system and its influences on human behavior. In the modern day, with the US facing an ongoing epidemic of substance use without an effective treatment, these investigations are of paramount importance. It is well known that basal ganglia contribute to rewards and are involved in learning, approach behavior, economic choices, and positive emotions. This review aims to elucidate the physiological role of striatonigrostriatal (SNS) spirals, as part of basal ganglia circuits, in this reward system and their pathophysiological role in perpetuating addiction. Additionally, the main functions of neurotransmitters such as dopamine and glutamate and their receptors in SNS circuits will be summarized. With this information, the claim that SNS spirals are crucial intermediaries in the shift from goal-directed behavior to habitual behavior will be supported, making this circuit a viable target for potential therapeutic intervention in those with substance use disorders.

scholarly journals Protease-activated receptor 2 exacerbates cisplatin-induced nephrotoxicity

2019 ◽  
Vol 316 (4) ◽  
pp. F654-F659 ◽  
Author(s):  
Mari Watanabe ◽  
Yuji Oe ◽  
Emiko Sato ◽  
Akiyo Sekimoto ◽  
Hiroshi Sato ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Factor Viia ◽  
Therapeutic Option ◽  
Factor Xa ◽  
Kidney Injury ◽  
Coagulation Cascade ◽  
Expression Levels ◽  
Cisplatin Nephrotoxicity ◽  
Protease Activated Receptor 2

Acute kidney injury (AKI) is associated with hypercoagulability. Tissue factor/factor VIIa complex and factor Xa in the coagulation cascade activate protease-activated receptor 2 (PAR2). Previously, we have shown that PAR2-mediated inflammation aggravates kidney injury in models of diabetic kidney disease and adenine-induced renal fibrosis. However, the role of PAR2 in AKI remains unclear. To clarify the role of PAR2, we administered cisplatin, one of the most common causal factors of AKI, to wild-type and PAR2-deficient mice. The expression levels of tissue factor and PAR2 were significantly increased in the kidneys of mice that were administered cisplatin. A lack of PAR2 corrected the levels of plasma blood urea nitrogen and creatinine as well as ameliorated the acute tubular injury score in the kidney. A lack of PAR2 corrected the infiltration of neutrophils and the gene expression levels of proinflammatory cytokines/chemokines in these mouse kidneys. Similarly, apoptotic markers, such as cleaved caspase-3-positive area and Bax/Bcl2 ratio, were attenuated via PAR2 deletion. Thus, elevated PAR2 exacerbates cisplatin nephrotoxicity, and targeting PAR2 is a novel therapeutic option that aids in the treatment of patients with cisplatin-induced AKI.

Abstract 190: Purinergic Control of Tissue Factor Transcription in Human Coronary Artery Endothelial Cells: New AP-1 Site and Negative Regulator

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yiwei Liu ◽  
Lingxin Zhang ◽  
Chuan Wang ◽  
Shama Roy ◽  
Jianzhong Shen
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Tissue Factor ◽  
Promoter Activity ◽  
Purinergic Receptor ◽  
Consensus Sequence ◽  
Negative Regulator ◽  
Coagulation Cascade ◽  
Human Coronary Artery

Previously we reported that the P2Y2 receptor (P2Y2R) is one of the predominant purinergic receptors expressed in human coronary artery endothelial cells (HCAEC), and that P2Y2R activation by ATP or UTP induces dramatic up-regulation of tissue factor (TF), key initiator of the coagulation cascade. However, the molecular mechanism of this P2Y2R-TF axis remains unclear. Here we report a role of a newly identified AP-1 consensus sequence along with its new binding components in P2Y2R regulation of TF transcription. We identified with bioinformatics tools that a novel AP-1 site at -1363 bp of human TF promoter region is highly conserved across multiple species. P2Y2R activation increased TF promoter activity and mRNA expression in HCAEC. Truncation, deletion, and mutation of this new distal AP-1 site all significantly supressed TF promoter activity in response to P2Y2R activation. EMSA and ChIP assays further confirmed that upon P2Y2R activation, c-Jun, ATF-2 and Fra-1, but not the typical c-Fos, bound to the new AP-1 site. In addition, loss-of-function studies using siRNAs confirmed a positive transactivation role of c-Jun and ATF-2, but unexpectedly revealed a strong negative role of Fra-1 in P2Y2R-induced TF up-regulation. Furthermore, we found that P2Y2R activation promoted ERK1/2 phosphorylation, leading to Fra-1 activation while JNK activated c-Jun and ATF-2. These findings reveal the basis for P2Y purinergic receptor regulation of endothelial TF expression and indicate that targeting the P2Y2R-Fra-1-TF pathway may be an attractive new strategy in control of vascular thrombogenicity and/or inflammation associated with endothelial dysfunction.

The potential pathophysiological role of tissue factor in age-related macular degeneration

2010 ◽  
Vol 5 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Youngeun Cho ◽  
Frederick R Rickles ◽  
Leonard M Parver ◽  
Jingsheng Tuo ◽  
Chi-Chao Chan
Keyword(s):  
Macular Degeneration ◽  
Tissue Factor ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Pathophysiological Role

Role of Tissue Factor in Tumor Progression and Cancer-Associated Thrombosis

2019 ◽  
Vol 45 (04) ◽  
pp. 396-412 ◽  
Author(s):  
Araci M. R. Rondon ◽  
Chantal Kroone ◽  
Maaike Y. Kapteijn ◽  
Henri H. Versteeg ◽  
Jeroen T. Buijs
Keyword(s):  
Tissue Factor ◽  
Cancer Progression ◽  
Coagulation Cascade ◽  
Clinical Phase ◽  
Transmembrane Glycoprotein ◽  
Cancer Models ◽  
Cytotoxic Compounds ◽  
Cancer Associated Thrombosis ◽  
Tumor Types

AbstractIt has been long-established that cancer and thrombosis are linked, but the exact underlying pathological mechanism remains to be unraveled. As the initiator of the coagulation cascade, the transmembrane glycoprotein tissue factor (TF) has been intensely investigated for its role in cancer-associated thrombosis and cancer progression. TF expression is regulated by both specific oncogenes and environmental factors, and it is shown to regulate primary growth and metastasis formation in a variety of cancer models. In clinical studies, TF has been shown to be overexpressed in most cancer types and is strongly associated with disease progression. While TF clearly associates with cancer progression, a prominent role for TF in the development of cancer-associated thrombosis is less clear. The current concept is that cancer-associated thrombosis is associated with the secretion of tumor-derived TF-positive extracellular vesicles in certain tumor types. To date, many therapeutic strategies to target TF—both in preclinical and clinical phase—are being pursued, including targeting TF or the TF:FVIIa complex by itself or by exploiting TF as a docking molecule to deliver cytotoxic compounds to the tumor. In this review, the authors summarize the current understanding of the role of TF in both cancer progression and cancer-associated thrombosis, and discuss novel insights on TF as a therapeutic target as well as a biomarker for cancer progression and VTE.

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