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Cellular Immunology 2014Monocyte development is a tightly regulated and multi-staged process, occurring through several defined progenitor cell intermediates. The key transcription factors,... (Review)
Review
Monocyte development is a tightly regulated and multi-staged process, occurring through several defined progenitor cell intermediates. The key transcription factors, including PU.1, IRF8 and KLF4, growth factors, such as M-CSF and IL-34 and cytokines that drive monocyte development from hematopoietic progenitor cells are well defined. However, the molecular controls that direct differentiation into the Ly6C(hi) inflammatory and Ly6C(lo) monocyte subsets are yet to be completely elucidated. This review will provide a summary of the transcriptional regulation of monocyte development. We will also discuss how these molecular controls are also critical for microglial development despite their distinct haematopoetic origins. Furthermore, we will examine recent breakthroughs in defining mechanisms that promote differentiation of specific monocyte subpopulations.
Topics: Animals; Cell Differentiation; Kruppel-Like Factor 4; Mice; Monocytes; Stem Cells; Transcription, Genetic
PubMed: 24709055
DOI: 10.1016/j.cellimm.2014.02.008 -
BioMed Research International 2020The brain is the most important and complex organ in most living creatures which serves as the center of the nervous system. The function of human brain includes... (Review)
Review
The brain is the most important and complex organ in most living creatures which serves as the center of the nervous system. The function of human brain includes controlling of the motion of the body and different organs and maintaining basic homeostasis. The disorders of the brain caused by a variety of reasons often severely impact the patients' normal life or lead to death in extreme cases. Monocyte is an important immune cell which is often recruited to the brain in a number of brain disorders. However, the role of monocytes may not be simply described as beneficial or detrimental. It significantly depends on the disease models and the stages of disease progression. In this review, we summarized the current knowledge about the role of monocytes and monocyte-derived macrophages during several common brain disorders. Major focuses include ischemic stroke, Alzheimer's disease, multiple sclerosis, intracerebral hemorrhage, and insomnia. The recruitment, differentiation, and function of monocyte in these diseases are reviewed.
Topics: Animals; Brain Diseases; Cell Differentiation; Humans; Inflammation; Macrophages; Mice; Monocytes
PubMed: 32596397
DOI: 10.1155/2020/9396021 -
Nature Reviews. Cardiology Jul 2017Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. Monocytes and macrophages are involved in cardiovascular... (Review)
Review
Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. Monocytes and macrophages are involved in cardiovascular disease progression, and are associated with the development of unstable atherosclerotic plaques. Hyperlipidaemia can accelerate cardiovascular disease progression. However, monocyte responses to hyperlipidaemia are poorly understood. In the past decade, accumulating data describe the relationship between the dynamic blood lipid environment and the heterogeneous circulating monocyte pool, which might have profound consequences for cardiovascular disease. In this Review, we explore the updated view of monocytes in cardiovascular disease and their relationship with macrophages in promoting the homeostatic and inflammatory responses related to atherosclerosis. We describe the different definitions of dyslipidaemia, highlight current theories on the ontogeny of monocyte heterogeneity, discuss how dyslipidaemia might alter monocyte production, and explore the mechanistic interface linking dyslipidaemia with monocyte effector functions, such as migration and the inflammatory response. Finally, we discuss the role of dietary and endogenous lipid species in mediating dyslipidaemic responses, and the role of these lipids in promoting the risk of cardiovascular disease through modulation of monocyte behaviour.
Topics: Cardiovascular Diseases; Dietary Fats; Dyslipidemias; Humans; Monocytes; Plaque, Atherosclerotic
PubMed: 28300081
DOI: 10.1038/nrcardio.2017.34 -
Frontiers in Immunology 2020Monocytes are a highly plastic innate immune cell population that displays significant heterogeneity within the circulation. Distinct patterns of surface marker... (Review)
Review
Monocytes are a highly plastic innate immune cell population that displays significant heterogeneity within the circulation. Distinct patterns of surface marker expression have become accepted as a basis for distinguishing three monocyte subsets in humans. These phenotypic subsets, termed classical, intermediate and nonclassical, have also been demonstrated to differ in regard to their functional properties and disease associations when studied and . Nonetheless, for the intermediate monocyte subset in particular, functional experiments have yielded conflicting results and some studies point to further levels of heterogeneity. Developments in genetic sequencing technology have provided opportunities to more comprehensively explore the phenotypic and functional differences among conventionally-recognized immune cell subtypes as well as the potential to identify novel subpopulations. In this review, we summarize the transcriptomic evidence in support of the existence of three separate monocyte subsets. We also critically evaluate the insights into subset functional distinctions that have been garnered from monocyte gene expression analysis and the potential utility of such studies to unravel subset-specific functional changes which arise in disease states.
Topics: GPI-Linked Proteins; Gene Expression Profiling; Humans; Immune System Diseases; Immunity, Innate; Immunophenotyping; Lipopolysaccharide Receptors; Monocytes; Receptors, IgG
PubMed: 32582174
DOI: 10.3389/fimmu.2020.01070 -
Cancer Research Mar 2014Growing understanding of the role of the tumor microenvironment in angiogenesis has brought monocyte-derived cells into focus. Monocyte subpopulations are an... (Review)
Review
Growing understanding of the role of the tumor microenvironment in angiogenesis has brought monocyte-derived cells into focus. Monocyte subpopulations are an increasingly attractive therapeutic target in many pathologic states, including cancer. Before monocyte-directed therapies can be fully harnessed for clinical use, understanding of monocyte-driven angiogenesis in tissue development and homeostasis, as well as malignancy, is required. Here, we provide an overview of the mechanisms by which monocytic subpopulations contribute to angiogenesis in tissue and tumor development, highlight gaps in our existing knowledge, and discuss opportunities to exploit these cells for clinical benefit.
Topics: Animals; Humans; Monocytes; Neoplasms; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 24556724
DOI: 10.1158/0008-5472.CAN-13-2825 -
Seminars in Immunopathology Mar 2014Monocytes are mononuclear circulating phagocytes that originate in the bone marrow and give rise to macrophages in peripheral tissue. For decades, our understanding of... (Review)
Review
Monocytes are mononuclear circulating phagocytes that originate in the bone marrow and give rise to macrophages in peripheral tissue. For decades, our understanding of monocyte lineage was bound to a stepwise model that favored an inverse relationship between cellular proliferation and differentiation. Sophisticated molecular and surgical cell tracking tools have transformed our thinking about monocyte topo-ontogeny and function. Here, we discuss how recent studies focusing on progenitor proliferation and differentiation, monocyte mobilization and recruitment, and macrophage differentiation and proliferation are reshaping knowledge of monocyte lineage in steady state and disease.
Topics: Animals; Cell Differentiation; Cell Lineage; Cell Proliferation; Chemotaxis, Leukocyte; Humans; Macrophages; Monocyte-Macrophage Precursor Cells; Monocytes; Phagocytes
PubMed: 24435095
DOI: 10.1007/s00281-013-0409-1 -
The American Journal of Pathology May 2020Monocyte rolling, adhesion, and transmigration across the endothelium are mediated by specific interactions between surface adhesion molecules. This process is... (Review)
Review
Monocyte rolling, adhesion, and transmigration across the endothelium are mediated by specific interactions between surface adhesion molecules. This process is fundamental to innate immunity and to inflammatory disease, including atherosclerosis, where monocyte egress into the intimal space is central to formation of fatty plaques. Monocytes are a heterogeneous population of three distinct subsets of cells, all of which play different roles in atherosclerosis progression. However, it is not well understood how interactions between different monocyte subsets and the endothelium are regulated. Furthermore, it is appreciated that endothelial adhesion molecules are heavily N-glycosylated, but beyond regulating protein trafficking to the cell surface, whether and if so how these N-glycans contribute to monocyte recruitment is not known. This review discusses how changes in endothelial N-glycosylation may impact vascular and monocytic inflammation. It will also discuss how regulating N-glycoforms on the endothelial surface may allow for the recruitment of specific monocyte subsets to sites of inflammation, and how further understanding in this area may lead to the development of glyco-specific therapeutics in the treatment of cardiovascular disease.
Topics: Animals; Cell Adhesion Molecules; Endothelial Cells; Glycosylation; Humans; Leukocyte Rolling; Monocytes; Polysaccharides
PubMed: 32084367
DOI: 10.1016/j.ajpath.2020.01.006 -
Arteriosclerosis, Thrombosis, and... Jul 2011Vascular inflammation is associated with and in large part driven by changes in the leukocyte compartment of the vessel wall. Here, we focus on monocyte influx during... (Review)
Review
Vascular inflammation is associated with and in large part driven by changes in the leukocyte compartment of the vessel wall. Here, we focus on monocyte influx during atherosclerosis, the most common form of vascular inflammation. Although the arterial wall contains a large number of resident macrophages and some resident dendritic cells, atherosclerosis drives a rapid influx of inflammatory monocytes (Ly-6C(+) in mice) and other monocytes (Ly-6C(-) in mice, also known as patrolling monocytes). Once in the vessel wall, Ly-6C(+) monocytes differentiate to a phenotype consistent with inflammatory macrophages and inflammatory dendritic cells. The phenotype of these cells is modulated by lipid uptake, Toll-like receptor ligands, hematopoietic growth factors, cytokines, and chemokines. In addition to newly recruited macrophages, it is likely that resident macrophages also change their phenotype. Monocyte-derived inflammatory macrophages have a short half-life. After undergoing apoptosis, they may be taken up by surrounding macrophages or, if the phagocytic capacity is overwhelmed, can undergo secondary necrosis, a key event in forming the necrotic core of atherosclerotic lesions. In this review, we discuss these and other processes associated with monocytic cell dynamics in the vascular wall and their role in the initiation and progression of atherosclerosis.
Topics: Animals; Apoptosis; Atherosclerosis; Disease Progression; Foam Cells; Humans; Inflammation; Inflammation Mediators; Lipid Metabolism; Macrophages; Monocytes; Necrosis; Phenotype; Signal Transduction
PubMed: 21677293
DOI: 10.1161/ATVBAHA.110.221127 -
Thrombosis Research Aug 2023Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue factor is expressed by monocyte subsets (classical,...
INTRODUCTION
Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue factor is expressed by monocyte subsets (classical, intermediate and non-classical) is unknown.
METHODS
Monocytic tissue factor surface expression was investigated during three conditions. Primary human monocytes and microvascular endothelial cell co-cultures were used for in vitro studies. Volunteers received a bolus of lipopolysaccharide (2 ng/kg) to induce endotoxemia. Patients with sepsis, or controls with critical illness unrelated to sepsis, were recruited from four intensive care units.
RESULTS
Contact with endothelium and stimulation with lipopolysaccharide reduced the proportion of intermediate monocytes. Lipopolysaccharide increased tissue factor surface expression on classical and non-classical monocytes. Endotoxemia induced profound, transient monocytopenia, along with activation of coagulation pathways. In the remaining circulating monocytes, tissue factor was up-regulated in intermediate monocytes, though approximately 60 % of individuals (responders) up-regulated tissue factor across all monocyte subsets. In critically ill patients, tissue factor expression on intermediate and non-classical monocytes was significantly higher in patients with established sepsis than among non-septic patients. Upon recovery of sepsis, expression of tissue factor increased significantly in classical monocytes.
CONCLUSION
Tissue factor expression in monocyte subsets varies significantly during health, endotoxemia and sepsis.
Topics: Humans; Monocytes; Endotoxemia; Thromboplastin; Thromboinflammation; Lipopolysaccharides; Sepsis
PubMed: 37263122
DOI: 10.1016/j.thromres.2023.05.018 -
Immunobiology Dec 2012Atherosclerosis has been characterized as an inflammatory process, in which monocytes and monocyte-derived macrophages are of paramount importance. Contrasting with... (Review)
Review
Atherosclerosis has been characterized as an inflammatory process, in which monocytes and monocyte-derived macrophages are of paramount importance. Contrasting with their established role in atherosclerosis, monocytes have not unanimously been found to predict cardiovascular events in large epidemiological studies. However, in these studies human monocyte heterogeneity has been largely overlooked so far. Three human monocyte subsets can be distinguished: classical CD14(++)CD16(-), intermediate CD14(++)CD16(+) and nonclassical CD14(+)CD16(++) monocytes. Of note, correct enumeration of subset counts requires appropriate staining and gating strategies that encompass a pan-monocytic marker (e.g. HLA-DR or CD86). In experimental studies on murine atherogenesis a monocyte subset-specific contribution to atherosclerosis has been established. However, major interspecies differences in atherogenesis itself, as well as in the immune system (including monocyte subset phenotype and distribution) preclude a direct extrapolation to human pathology. Experimental and pilot clinical studies point to a prominent involvement of intermediate CD14(++)CD16(+) monocytes in human atherosclerosis. Future clinical studies should analyze monocyte heterogeneity in cardiovascular disease. If a specific contribution of intermediate monocytes should be confirmed, immunomodulation of this monocyte subset could represent a future therapeutic target in atherosclerosis.
Topics: Animals; Cardiovascular Diseases; Humans; Monocytes
PubMed: 22898391
DOI: 10.1016/j.imbio.2012.07.001