scholarly journals The Role of Monocytes Cellular and Molecular Mechanisms in the Development of Systemic Immune Inflammation. Part 1

Psychiatry ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 76-85
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Cognitive Disorders ◽  
Research Data ◽  
Vascular Endothelial ◽  
Platelet Aggregates ◽  
Immune Inflammation ◽  
The Brain

Introduction: the important role of monocytes /macrophages, as well as cytokines produced by them was determined in the pathogenesis of mental disorders, as a macrophage-T-lymphocyte theory of bipolar disorder, schizophrenia and depression. According to this theory, there is an increase in the number of active circulating monocytes, macrophages and T-cells in patients with mental disorders. These cells migrate to the CNS as a result of the blood-brain barrier breach, destabilize the brain and lead to worsening of mental disorders.The aim of work: to review research data on the role of proinflammator monocytes in the development of immune inflammation in the pathogenesis of a number of systemic diseases and to examine the molecular mechanisms mediating the interaction of proinflammatory monocytes with other cells involved in immune inflammation.Material and methods: keywords “proinflammatory monocyte CD16+”, “cytokines”, “molecules of cell adhesion”, “monocyte-platelet aggregates”, “microglia”, “psychiatriс disorders”, are used to search for data published over the past 20 years in domestic and foreign studies in PubMed and e-Library.Conclusion: in the first part of the review, the research data concerning the studies of the functional characteristics of a monocytes subpopulation that express on their surface an increased level of CD16 receptors when activated were analyzed. Most of researchers associate the proinflammatory functions of monocytes with this subpopulation. Molecular mechanisms of monocytes activation, which include increased secretion of CD16 receptors, cytokines, chemokines and receptors for them involved in their interaction with vascular endothelial cells, with neurons in the CNS and also with platelets in the development of systemic inflammation, are considered. Analysis of these mechanisms allows us to better understand the immune aspects of inflammation in the brain mediated by the interaction of CD16+ monocytes with neuronal cells, which results in cognitive disorders in patients with mental disorders, as well as to identify related new approaches to the treatment of cognitive decline in these patients. Studies of the monocyte unit of immunity in patients with mental disorders will be covered in the second part of the review.

scholarly journals Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 2

Psychiatry ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 81-92
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Mental Disorders ◽  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Psychotic Disorders ◽  
Bipolar Affective Disorder ◽  
Research Data ◽  
Scientific Publications ◽  
Somatic Comorbidity ◽  
Immune Inflammation

Introduction: at the end of the last century, the macrophage-T-lymphocyte theory of the development of mental disorders was formulated. It underlines the important role of monocytes/macrophages and cytokines produced by them in the pathogenesis of schizophrenia, bipolar affective disorder (BAD) and depression. The first part of our review is dedicated to the analysis of the mechanisms of cellular and molecular interactions of activated monocytes/macrophages synthesizing proinflammatory CD16 receptors with endothelial cells, platelets, and microglia cells in the pathogenesis of systemic immune inflammation, including CNS as a result of violation of the integrity of the blood-brain barrier (BBB), activate microglia and cause the development of neuroinflammation in patients.The aim of work: to analyze and summarize the results of the main scientific publications for the role of cell-molecular mechanisms of the monocyte-macrophage immunity link activation in the pathogenesis of schizophrenia, BAD and depression. Material and methods: keywords “proinflammatory monocytes, cytokines, chemokines, molecules of cell adhesion, microglia, neuroinflammation, mental disorders” were used to search for data published over the past 20 years in domestic and foreign studies in PubMed, eLIBRARY, Science direct and EMBASE.Conclusion: the present review is dedicated to the analysis of the latest research data concerning an increase in the number of active circulating monocytes/macrophages and an increased level of proinflammatory cytokines, chemokines and receptors for them produced by monocytes in patients with schizophrenia, BAD and depression, what allows to associate these disorders with systemic immune inflammation. The data reasearches on cellular and molecular mechanisms of proinflammatory monocytes/macrophages interaction with microglia cells that initiate neuroinflammation in the CNS and lead to destabilization of brain function and the development of psychotic disorders are presented. The association of high levels of proinflammatory cytokines with somatic comorbidity, including metabolic syndrome, diabetes, atherosclerosis and other systemic diseases is shown in patients with mental disorders.Findings: the presented review of the research data allows us to better understand the cellular and molecular aspects of activation of the monocyte-macrophage immunity link in the development of neuroinflammation and cognitive decline in the pathogenesis of mental disorders, as well as helps in the search for informative biomarkers of the positive treatment of these disorders and the new approaches in the treatment of patients, based on the complex use of psychotropic and anti-inflammatory drugs.

Effect of Neuroinflammation on ABC Transporters: Possible Contribution to Refractory Epilepsy

2018 ◽  
Vol 17 (10) ◽  
pp. 728-735 ◽  
Author(s):  
Xiaolin Deng ◽  
Yangmei Xie ◽  
Yinghui Chen
Keyword(s):  
Antiepileptic Drugs ◽  
Abc Transporters ◽  
Refractory Epilepsy ◽  
Vascular Endothelial Cells ◽  
Efflux Transporters ◽  
Vascular Endothelial ◽  
Intracellular Signalling Pathways ◽  
The Brain ◽  
Transporter Expression

Background & Objective: Epilepsy is a common and serious chronic neurological disorder that is mainly treated with antiepileptic drugs. Although current antiepileptic drugs used in clinical practice have advanced to the third generation, approximately one-third of patients are refractory to these treatments. More efficacious treatments for refractory epilepsy are therefore needed. A better understanding of the mechanism underlying refractory epilepsy is likely to facilitate the development of a more effective therapy. The abnormal expression and/or dysfunction of efflux transporters, particularly ABC transporters, might contribute to certain cases of refractory epilepsy. Inflammation in the brain has recently been shown to regulate the expression and/or function of ABC transporters in the cerebral vascular endothelial cells and glia of the blood-brain barrier by activating intracellular signalling pathways. Conclusion: Therefore, in this review, we will briefly summarize recent research advances regarding the possible role of neuroinflammation in regulating ABC transporter expression in epilepsy.

Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 3

Psychiatry ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 125-134
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Microglial Cells ◽  
Inflammatory Reactions ◽  
Mental Diseases ◽  
The Central Nervous System ◽  
The Brain

Background: at present, the important role of the monocyte-macrophage link of immunity in the pathogenesis of mental diseases has been determined. In the first and second parts of our review, the cellular and molecular mechanisms of activation of monocytes/macrophages, which secreting proinflammatory CD16 receptors, cytokines, chemokines and receptors to them, in the development of systemic immune inflammation in the pathogenesis of somatic diseases and mental disorders, including schizophrenia, bipolar affective disorder (BAD) and depression were analyzed. The association of high levels of proinflammatory activity of monocytes/macrophages in patients with mental disorders with somatic comorbidity, including immune system diseases, is shown. It is known that proinflammatory monocytes of peripheral blood, as a result of violation of the integrity of the hematoencephalic barrier can migrate to the central nervous system and activate the resident brain cells — microglia, causing its activation. Activation of microglia can lead to the development of neuroinammation and neurodegenerative processes in the brain and, as a result, to cognitive disorders. The aim of review: to analyze the results of the main scientific studies concerning the role of cellular and molecular mechanisms of peripheral blood monocytes interaction with microglial cells and platelets in the development of neuroinflammation in the pathogenesis of mental disorders, including Alzheimer’s disease (AD). Material and methods: keywords “mental disorders, AD, proinflammatory monocytes, microglia, neuroinflammation, cytokines, chemokines, cell adhesion molecules, platelets, microvesicles” were used to search for articles of domestic and foreign authors published over the past 30 years in the databases PubMed, eLibrary, Science Direct and EMBASE. Conclusion: this review analyzes the results of studies which show that monocytes/macrophages and microglia have similar gene expression profiles in schizophrenia, BAD, depression, and AD and also perform similar functions: phagocytosis and inflammatory responses. Monocytes recruited to the central nervous system stimulate the increased production of proinflammatory cytokines IL-1, IL-6, tumor necrosis factor alpha (TNF-α), chemokines, for example, MCP-1 (Monocyte chemotactic protein-1) by microglial cells. This promotes the recruitment of microglial cells to the sites of neuronal damage, and also enhances the formation of the brain protein beta-amyloid (Aβ). The results of modern studies are presented, indicating that platelets are involved in systemic inflammatory reactions, where they interact with monocytes to form monocyte-platelet aggregates (MTA), which induce the activation of monocytes with a pro inflammatory phenotype. In the last decade, it has been established that activated platelets and other cells of the immune system, including monocytes, detached microvesicles (MV) from the membrane. It has been shown that MV are involved as messengers in the transport of biologically active lipids, cytokines, complement, and other molecules that can cause exacerbation of systemic inflammatory reactions. The presented review allows us to expand our knowledge about the cellular and molecular aspects of the interaction of monocytes/macrophages with microglial cells and platelets in the development of neuroinflammation and cognitive decline in the pathogenesis of mental diseases and in AD, and also helps in the search for specific biomarkers of the clinical severity of mental disorder in patients and the prospects for their response to treatment.

scholarly journals Molecular Dambusters: What Is Behind Hyperpermeability in Bradykinin-Mediated Angioedema?

2021 ◽  
Author(s):  
Márta L. Debreczeni ◽  
Zsuzsanna Németh ◽  
Erika Kajdácsi ◽  
Henriette Farkas ◽  
László Cervenak
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Edema Formation ◽  
Endothelial Cell Function ◽  
Number Of Factors ◽  
Complex Scenario

AbstractIn the last few decades, a substantial body of evidence underlined the pivotal role of bradykinin in certain types of angioedema. The formation and breakdown of bradykinin has been studied thoroughly; however, numerous questions remained open regarding the triggering, course, and termination of angioedema attacks. Recently, it became clear that vascular endothelial cells have an integrative role in the regulation of vessel permeability. Apart from bradykinin, a great number of factors of different origin, structure, and mechanism of action are capable of modifying the integrity of vascular endothelium, and thus, may participate in the regulation of angioedema formation. Our aim in this review is to describe the most important permeability factors and the molecular mechanisms how they act on endothelial cells. Based on endothelial cell function, we also attempt to explain some of the challenging findings regarding bradykinin-mediated angioedema, where the function of bradykinin itself cannot account for the pathophysiology. By deciphering the complex scenario of vascular permeability regulation and edema formation, we may gain better scientific tools to be able to predict and treat not only bradykinin-mediated but other types of angioedema as well.

scholarly journals The emerging role of cell senescence in atherosclerosis

2021 ◽  
Vol 59 (1) ◽  
pp. 27-38 ◽  
Author(s):  
Chang-Meng Wu ◽  
Lei Zheng ◽  
Qian Wang ◽  
Yan-Wei Hu
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Cell Types ◽  
Cell Senescence ◽  
Vascular Endothelial ◽  
Monocyte Chemoattractant Protein 1 ◽  
Plaque Instability ◽  
Inflammatory Molecules ◽  
Progression Of Atherosclerosis

AbstractCell senescence is a fundamental mechanism of aging and appears to play vital roles in the onset and prognosis of cardiovascular disease, fibrotic pulmonary disease, liver disease and tumor. Moreover, an increasing body of evidence shows that cell senescence plays an indispensable role in the formation and development of atherosclerosis. Multiple senescent cell types are associated with atherosclerosis, senescent human vascular endothelial cells participated in atherosclerosis via regulating the level of endothelin-1 (ET-1), nitric oxide (NO), angiotensin II and monocyte chemoattractant protein-1 (MCP-1), senescent human vascular smooth muscle cells-mediated plaque instability and vascular calcification via regulating the expression level of BMP-2, OPN, Runx-2 and inflammatory molecules, and senescent macrophages impaired cholesterol efflux and promoted the development of senescent-related cardiovascular diseases. This review summarizes the characteristics of cell senescence and updates the molecular mechanisms underlying cell senescence. Moreover, we also discuss the recent advances on the molecular mechanisms that can potentially regulate the development and progression of atherosclerosis.

scholarly journals Dual Role of Jam3b in Early Hematopoietic and Vascular Development

2019 ◽  
Author(s):  
Isao Kobayashi ◽  
Jingjing Kobayashi-Sun ◽  
Yuto Hirakawa ◽  
Madoka Ouchi ◽  
Koyuki Yasuda ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Signaling Cascade ◽  
Vascular Endothelial ◽  
Lateral Plate ◽  
Hematopoietic Stem

AbstractIn order to efficiently derive hematopoietic stem cells (HSCs) from pluripotent precursors, it is crucial to understand how mesodermal cells acquire hematopoietic or endothelial identity due to their close developmental connection. Although Npas4 has been recently identified as a conserved master regulator of hemato-vascular development, the molecular mechanisms underlying the cell fate divergence between hematopoietic and vascular endothelial cells are still unclear. Here, we show in zebrafish that the divergence of hematopoietic and vascular endothelial cells in mesodermal cells is regulated by Junctional adhesion molecule 3b (Jam3b) via two independent signaling pathways. Mutation of jam3b led to the reduction of npas4l expression in the posterior lateral plate mesoderm and defect of both hematopoietic and vascular development. Mechanistically, we uncover that Jam3b promotes endothelial specification by regulating npas4l expression through the repression of the Rap1a-Erk signaling cascade. Jam3b subsequently promotes hematopoietic development including HSCs by regulating lrrc15 expression in endothelial precursors through the activation of an integrin-dependent signaling cascade. Our data provide insight into the divergent mechanisms for instructing hematopoietic or vascular fates from mesodermal cells.

scholarly journals Emerging Role of AP-1 Transcription Factor JunB in Angiogenesis and Vascular Development

2021 ◽  
Vol 22 (6) ◽  
pp. 2804
Author(s):  
Yasuo Yoshitomi ◽  
Takayuki Ikeda ◽  
Hidehito Saito-Takatsuji ◽  
Hideto Yonekura
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Blood Vessel Formation ◽  
Vessel Formation

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.

scholarly journals First blood: the endothelial origins of hematopoietic progenitors

Angiogenesis ◽  
2021 ◽  
Author(s):  
Giovanni Canu ◽  
Christiana Ruhrberg
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Fetal Liver ◽  
Cell Types ◽  
Yolk Sac ◽  
Vascular Endothelial ◽  
Hematopoietic Stem ◽  
Close Proximity ◽  
Clinical Interest

AbstractHematopoiesis in vertebrate embryos occurs in temporally and spatially overlapping waves in close proximity to blood vascular endothelial cells. Initially, yolk sac hematopoiesis produces primitive erythrocytes, megakaryocytes, and macrophages. Thereafter, sequential waves of definitive hematopoiesis arise from yolk sac and intraembryonic hemogenic endothelia through an endothelial-to-hematopoietic transition (EHT). During EHT, the endothelial and hematopoietic transcriptional programs are tightly co-regulated to orchestrate a shift in cell identity. In the yolk sac, EHT generates erythro-myeloid progenitors, which upon migration to the liver differentiate into fetal blood cells, including erythrocytes and tissue-resident macrophages. In the dorsal aorta, EHT produces hematopoietic stem cells, which engraft the fetal liver and then the bone marrow to sustain adult hematopoiesis. Recent studies have defined the relationship between the developing vascular and hematopoietic systems in animal models, including molecular mechanisms that drive the hemato-endothelial transcription program for EHT. Moreover, human pluripotent stem cells have enabled modeling of fetal human hematopoiesis and have begun to generate cell types of clinical interest for regenerative medicine.

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