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.

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.

scholarly journals Nonneuronal Cholinergic System in Breast Tumors and Dendritic Cells: Does It Improve or Worsen the Response to Tumor?

2013 ◽  
Vol 2013 ◽  
pp. 1-12
Author(s):  
Marisa Vulcano ◽  
María Gabriela Lombardi ◽  
María Elena Sales
Keyword(s):  
Dendritic Cells ◽  
Cholinergic System ◽  
Parasympathetic Nervous System ◽  
Immune Cell ◽  
Breast Tumors ◽  
Cell Types ◽  
Cellular Functions ◽  
And Migration ◽  
And Function

Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.

scholarly journals Revealing the enigma of coagulation in endometriosis: the risk of thrombosis and the role of antithrombotic treatment

2020 ◽  
Vol 19 (2) ◽  
pp. 65-76
Author(s):  
Theoni Kanellopoulou
Keyword(s):  
Independent Risk Factor ◽  
Chronic Inflammatory Disease ◽  
Review Article ◽  
Reproductive Age ◽  
Coagulation Cascade ◽  
Antithrombotic Treatment ◽  
Women Of Reproductive Age ◽  
The Relationship ◽  
Ectopic Endometrium

Endometriosis is a chronic inflammatory disease of women of reproductive age that is defined by the presence of ectopic endometrium. The pathophysiology of the disease is poorly understood, however platelet activation play a crucial role in initiation of inflammation and fibrinogenesis, which in term further activate the coagulation cascade. The relationship between inflammation and coagulation motivated researchers to study whether patients are in a hypercoagulable state and if endometriosis represent an independent risk factor for venous thromboembolism or cardiovascular risk. This review article focuses on the role of coagulation, the risk of thrombosis and a possible beneficial effect of antithrombotic-treatment.

scholarly journals THE ROLE OF INFLAMMATION AND COAGULATION CASCADE IN THE PATHOGENESIS OF ATRIAL FIBRILLATION

ASJ. ◽  
2020 ◽  
Vol 3 (41) ◽  
pp. 8-10
Author(s):  
L. Hazarapetyan ◽  
S. Grigoryan ◽  
A. Sarksyan
Keyword(s):  
Atrial Fibrillation ◽  
Coagulation Cascade ◽  
Control Group ◽  
Atrial Remodeling ◽  
Inflammation Markers ◽  
Reactive Protein ◽  
Gender And Age ◽  
The Impact ◽  
The Relationship

Introduction: Atrial fibrillation (AF) is associated with prothrombotic or hypercoagulable states, various inflammation markers such as interleukin-6 (IL-6) and hsC-reactive protein (hsCRP) have also been associated with AF. The aim of this study is to investigate the relationship between inflammation markers and the prothrombotic state in the setting of AF and the impact on outcome in patients with AF. Methods: We observed 141 patients with non-valvular AF. As a control group patients similar in gender and age without AF were examined. Clinical, instrumental and laboratory tests were performed on the observed patients. The markers of the coagulation cascade (TF and F) and of inflammatory markers (hsCRP and IL-6) were studied additionally by ELISA on the analyzer "Stat Fax 303 Plus". Studies were conducted using SPSS 13.0 and EXCEL-2013. Results: The obtained results showed that compared to the control group, AF patients had significantly higher levels of IL-6 (p = 0.043), hsCRP (p = 0.002), TF (p = 0.026), and F (p = 0.025). Moreover, levels of hsCRP were higher among AF patients at "high" risk of stroke by CHA2DS2-VASc Score (p = 0.003). Besides, the levels of hsCRP and IL-6 were markedly elevated in patients with dilated left atrium (p = 0.001), poorly functioning left atrial appendage (p = 0.023) and longer duration of AF (p = 0.002). Conclusion: We have demonstrated that the increased plasma levels of IL-6 and hsCRP are related to indices of the coagulation cascade and contribute to structural atrial remodeling in patients with AF.

scholarly journals Medical and Surgical Management of Postpartum Hemorrhage in a Woman with Factor XIII Deficiency

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Michael Cheng ◽  
Janelle Nassim ◽  
Ario Angha ◽  
Krisna Srey ◽  
Alexander Canales ◽  
...  
Keyword(s):  
Surgical Management ◽  
Postpartum Hemorrhage ◽  
Factor Xiii ◽  
Surgical Intervention ◽  
Coagulation Cascade ◽  
Clotting Factor ◽  
Factor Xiii Deficiency ◽  
Spontaneous Vaginal Delivery ◽  
Intraoperative Management ◽  
Emergency Surgical Intervention

Factor XIII deficiency is a rare inherited coagulopathy. Factor XIII is the last clotting factor in the coagulation cascade to insure strength and stability to fibrin clots. Without this enzyme, the fibrous clot is unstable and nonresistant to fibrinolysis. Gravid women with this congenital disease are especially at risk for complications including miscarriages and hemorrhage without appropriate interventions. We present a case of a woman in her 20s with Factor XIII deficiency who was treated with cryoprecipitate and had a successful normal spontaneous vaginal delivery; subsequently, patient suffered from postpartum hemorrhage and consumptive coagulopathy due to consumption of Factor XIII, requiring emergency surgical intervention. Intraoperative management was challenged by an ethical dilemma involving the patient’s religious beliefs about not receiving blood. This paper will discuss the mechanism of Factor XIII and the medical and surgical management involved with this patient.

scholarly journals Role of Deubiquitinases in Human Cancers: Potential Targeted Therapy

2020 ◽  
Vol 21 (7) ◽  
pp. 2548 ◽  
Author(s):  
Keng Po Lai ◽  
Jian Chen ◽  
William Ka Fai Tse
Keyword(s):  
Posttranslational Modifications ◽  
Cancer Biology ◽  
Cell Cycle Control ◽  
Basic Knowledge ◽  
Cellular Functions ◽  
Human Cancers ◽  
Downstream Effectors ◽  
Damage Response ◽  
The Relationship

Deubiquitinases (DUBs) are involved in various cellular functions. They deconjugate ubiquitin (UBQ) from ubiquitylated substrates to regulate their activity and stability. Studies on the roles of deubiquitylation have been conducted in various cancers to identify the carcinogenic roles of DUBs. In this review, we evaluate the biological roles of DUBs in cancer, including proliferation, cell cycle control, apoptosis, the DNA damage response, tumor suppression, oncogenesis, and metastasis. This review mainly focuses on the regulation of different downstream effectors and pathways via biochemical regulation and posttranslational modifications. We summarize the relationship between DUBs and human cancers and discuss the potential of DUBs as therapeutic targets for cancer treatment. This review also provides basic knowledge of DUBs in the development of cancers and highlights the importance of DUBs in cancer biology.

SKIN INFECTIONS AND ACUTE NEPHRITIS IN AMERICAN INDIAN CHILDREN

PEDIATRICS ◽  
1967 ◽  
Vol 39 (2) ◽  
pp. 263-279
Author(s):  
Bascom F. Anthony ◽  
Lawrence V. Perlman ◽  
Lewis W. Wannamaker
Keyword(s):  
Normal Population ◽  
Skin Lesions ◽  
Skin Infections ◽  
Upper Respiratory Tract ◽  
Indian Children ◽  
Superficial Skin ◽  
Group A ◽  
Relationship Of ◽  
The Relationship

Serial observations were obtained over an 18-month period of 270 Indian children with pyoderma. Beta-hemolytic streptococci, predominantly group A, and coagulasepositive staphylococci were recovered from the majority of lesions (80% and 70%, respectively), both on the initial and on subsequent cultures. The predominant agglutination patterns of streptococcal strains were similar to those described in other studies of superficial skin infections. Another agglutination pattern, 17/23/47, not previously observed to be prevalent in streptococci from skin lesions, was identified in a significant number of skin cultures. In addition, the hitherto undescribed association of M-types, including type 41 and a new M-type, with strains of T-agglutination pattern 3/13/B3264 was found. In striking contrast to the streptococcal strains, established "impetigo" strains of Staph. aureus (type 71 or other group II strains) were in the minority. Throat cultures of children with pyoderma suggested a limited relationship between infection or colonization of the pharynx and infection of the skin, while nasal streptococci were more closely correlated with and possibly derived from the flora of the skin lesions. Titers of ASO were not often elevated over control values in children with pyoderma, while anti-DNAse B titers were more commonly increased. Group A streptococci isolated from skin lesions prior to or at the time acute nephritis was recognized included type 12 (M and T) and strains classified by T-agglutination as 5/27/44, 11 and 4. The role of infection or colonization of the upper respiratory tract in the relationship of pyoderma to nephritis was not clarified in these studies. Moreover, in view of the frequency of change of group A streptococcal strains in skin lesions, as shown in serial observations in this study, the nephritogenic significance of streptococci recovered from skin lesions at the time of recognition of nephritis must remain in some doubt. Questions concerning the pathogenesis of endemic nephritis associated with pyoderma can probably be most reliably answered by frequent, prospective observations of a normal population with significant occurrence of streptococcal skin infections.

Tissue Factor Internalization and Trafficking in Fibroblasts: Involvement of Protease Activated Receptors-Mediated Cell Signaling.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 541-541
Author(s):  
Samir K. Mandal ◽  
Usha R. Pendurthi ◽  
L. Vijaya Mohan Rao
Keyword(s):  
Cell Surface ◽  
Cell Signaling ◽  
Tissue Factor ◽  
Protease Activity ◽  
Lung Epithelial Cells ◽  
Lung Fibroblasts ◽  
Coagulation Cascade ◽  
Clotting Factor ◽  
Outer Cell

Abstract Tissue factor (TF) is the cellular receptor for clotting factor VIIa (FVIIa) and the formation of TF-FVIIa complexes on cell surfaces triggers the activation of coagulation cascade and cell signaling. TF is constitutively expressed in many extravascular cells, including fibroblasts and pericytes in and surrounding blood vessel walls, and lung epithelial cells. Our recent studies (Blood2006; 107:4746–4753) show that a majority of TF resides in various intracellular compartments, predominantly in the Golgi. FVIIa binding to cell surface TF induces the internalization of TF, and interestingly, mobilizes the Golgi TF pool and transports it to the outer cell surface. This process is dependent on FVIIa protease activity. This present study is aimed to elucidate potential mechanisms involved in TF internalization and the mobilization from the Golgi. Since studies from our laboratory and others showed that TF-FVIIa could activate protease-activated receptor (PAR)-mediated cell signaling and FVIIa protease activity is required for FVIIa-dependent internalization and trafficking of TF, we hypothesize that TF-VIIa activation of PAR1 or PAR2 plays a role in TF internalization and trafficking. To test this hypothesis, we first examined the role of PAR activation in TF-internalization and trafficking. Lung fibroblasts (WI-38 cells) were exposed to a variety of PAR activators, PAR activating peptide agonists (AP) and various proteases, and TF internalization and trafficking was evaluated by measuring the cell surface TF antigen and activity levels, internalization of cell surface TF (by using biotinylation of cell surface receptors and immunoprecipitation techniques) and mobilization of TF from the Golgi (by immunofluorescence confocal microscopy). PAR1 AP and PAR2 AP treatments increased the TF activity and antigen levels at the cell surface by 20 to 50% whereas PAR3 AP and PAR4 AP had no effect on cell surface TF activity and antigen levels. Cell surface TF activity and antigen levels were also increased slightly in fibroblasts exposed to thrombin and trypsin. Confocal microscopic image analysis of distribution of TF and the Golgi protein (golgin-97) revealed that about 85% of the untreated cells possess intact Golgi TF pool with high degree of colocalization with golgin-97 whereas as only 20–30% of FVIIa, thrombin, trypsin, PAR1 AP or PAR2 AP-treated cells had TF pool in the Golgi. Plasmin and FXa had moderate effect on TF mobilization from the Golgi. No detectable differences were found between control (untreated) cells and cells treated with either FFR-FVIIa, APC, PAR3 AP or PAR4 AP. Next, we investigated the role of PAR1 and PAR2 activation in FVIIa-mediated TF internalization and trafficking. Pretreatment of fibroblasts with PAR2 but not PAR1 activation blocking antibodies attenuated FVIIa-mediated Golgi TF mobilization. Consistent with these data, silencing PAR2 receptor by siRNA technique completely blocked FVIIa-mediated Golgi TF mobilization whereas PAR1 siRNA transfection had no effect (in control studies, we showed PAR1 antibodies or PAR1si RNA transfection blocked thrombin-mediated TF mobilization). Additional studies showed a significant internalization of TF in cells exposed to FVIIa which was completely blocked by silencing PAR2 but not PAR1. Overall the data provided herein suggest a novel mechanism by which tissue factor expression is regulated at the cell surface.

scholarly journals A Comprehensive Investigation to Reveal the Relationship Between Plasmacytoid Dendritic Cells and Breast Cancer by Multiomics Data Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Saisai Tian ◽  
Li Yan ◽  
Lu Fu ◽  
Zhen Zhang ◽  
Jinbo Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dendritic Cells ◽  
Data Analysis ◽  
Plasmacytoid Dendritic Cells ◽  
Copy Number Alterations ◽  
Immune Microenvironment ◽  
Comprehensive Investigation ◽  
The Relationship ◽  
Somatic Copy Number Alterations

Plasmacytoid dendritic cells (pDC) are an essential immune microenvironment component. They have been reported for crucial roles in linking the adaptive and immune systems. However, the prognostic role of the pDC in breast cancer (BRCA) was controversial. In this work, we collected large sample cohorts and did a comprehensive investigation to reveal the relationship between pDC and BRCA by multiomics data analysis. Elevated pDC levels were correlated with prolonged survival outcomes in BRCA patients. The distinct mutation landscape and lower burden of somatic copy number alterations (SCNA) and lower intratumoral heterogeneity were observed in the high pDC abundance group. Additionally, a more sensitive immune response and chemotherapies response were observed in the high pDC group, which implicates that patients with high pDC abundance can be benefited from the combination of chemotherapy and immunotherapy. In conclusion, the correlation between pDC abundance and BRCA patients’ overall survival (OS) was found to be positive. We identified the molecular profiles of BRCA patients with pDC abundance. Our findings may be beneficial in aiding in the development of immunotherapy and elucidating on the precision treatment for BRCA.

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