Clinical significance of monocyte heterogeneity pdf paperity. Monocytes display immunophenotypic heterogeneity with functionally distinct subpopulations. In lesions in which the inflammatory stimulus is persistent, these ly6c high monocyte derived macrophages remain inflammatory by expressing il1. Monocyte and macrophage heterogeneity in the heart circulation. Monocytes are mononuclear leukocytes that circulate in the blood and differentiate into macrophages and dcs dendritic cells. After birth, bone marrow derived blood monocytes re. Modulation of mannosyl, fucosyl receptor activity in vitro by lymphokines, gamma and alpha interferons, and dexamethasone. Colony stimulating factors and macrophage heterogeneity.
As the lung microenvironment is challenged and remodelled by inhaled pathogens and air particles, so is the alveolar macrophage pool altered by signals that maintain and or replace its composition. Interestingly, in 2003, an obesityassociated macrophage accumulation in adipose tissue has been described in mice. The nature of monocyte macrophage heterogeneity is also difficult to assess due to the considerable plasticity of macrophages, their repertoire of receptors and extensive biosynthetic capacity. Monocytes exist in at least two subsets, which are committed to divergent functions. Additionally new macrophage tracers could be designed to replace 18ffluorodeoxyglucose fdg as a more cell specific tracer in petct scans. The features of monocyte to macrophage transition and the full spectrum of macrophage activation states during either plaque progression or regression, however, are incompletely established. Hamilton arthritis and inflammation research centre, department of medicine, the university of melbourne. M1 macrophages result from classic monocyte activation in response to proinflammatory stimuli, such as ifn. However, all three monocyte subsets regardless of blood or synovial origin express an increased level of tlr9. The contributions of lung macrophage and monocyte heterogeneity to influenza pathogenesis article in immunology and cell biology 953 september 2016 with 81 reads how we measure reads. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. While intratumoral accumulation of nanomedicines combined with immunomodulation would significantly enhance therapeutic efficacy, such potential is challenged by the compressed environment and distinct.
Ykl40 is a macrophagederived factor that serves as a. The inner region of solid tumors is found to be highpressure, hypoxic, and immunosuppressive, providing a breeding ground for tumor aggressiveness and metastasis. University of groningen monocyte and macrophage heterogeneity. Here, we summarize recent findings in monocyte heterogeneity and their differentiation into dendritic cells, macrophages, and osteoclasts. While intratumoral accumulation of nanomedicines combined with immunomodulation would significantly enhance therapeutic efficacy, such potential is challenged by the compressed environment and distinct heterogeneity of the tumor. Furthermore, it is important not to overinterpret the expression of a single marker, such as cd11c, as indicative of dc differentiation. Noninvasive leukocyte imaging answered questions about how monocyte and macrophage content in the infarct influences left ventricular remodeling and the evolution of heart failure. Alveolar macrophages are tissueresident cells that line the inner epithelial surface of the alveoli and play a crucial role in lung development, surfactant homeostasis and immune surveillance. Pdf monocyte and macrophage heterogeneity siamon gordon. A infarct site inflammatory cell populations expand rapidly following ami with an initial expansion of ly6c high monocytes, peaking day 35, followed by an expansion of ly6c low macrophages, peaking on day 7. The discovery of the heterogeneity of the monocyte and macrophage populations caused new studies of the structure and functions of these cells 20. Both cd16 and cd206 have been adopted as surface markers indicative of macrophage activation or monocytetomacrophage maturation. Our findings reveal differential recruitment of macrophages with moleculartargeted versus radiation.
Unravelling mononuclear phagocyte heterogeneity nature. Both may be useful but these cells became valid diagnostic tools only when monocyte subsets are determined. Monocyte heterogeneity consequences for monocytederived. The heterogeneity of ly6chi monocytes controls their. Both cd16 and cd206 have been adopted as surface markers indicative of macrophage activation or monocyte to macrophage maturation. Sep 23, 2019 here, we give an overview of the stateoftheart research regarding mirnas that are differentially expressed between monocyte subsets and how they influence monocyte functional heterogeneity in health and disease, with descriptions of specific mirnas. Heterogeneous expression of apolipoproteine by human.
Only a few decades ago, students of the pathophysiology of cardiovascular disease paid little heed to the involvement of inflammation and immunity. For example, monocyte progenitor release from the bone marrow after coronary ligation in mice depends on. It is well known that macrophages in tissue may display considerable heterogeneity in response to cues from the environment. Finally, from a perspective of monocyte and macrophage heterogeneity, precise lineage relationships between these cells and their subsets have yet to be determined in the steady state as well as in the diseased heart. Tlr2 and tlr9 triggering pathways on these monocyte subsets stimulated the production of proinflammatory cytokines il1. The contributions of lung macrophage and monocyte heterogeneity to influenza pathogenesis article in immunology and cell biology 953 september 2016 with 81.
Monocyte differentiation and macrophage polarization. The features of monocytetomacrophage transition and the full spectrum of macrophage activation states during either plaque progression or regression, however, are incompletely established. Taylor abstract heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. Tissue macrophages, monocytes, macrophages, heterogeneity, phenotype, markers. Macrophage plasticity in response to gmcsf and csf1.
The role of macrophages in medulloblastoma, the most common malignant pediatric brain tumor, is unclear. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Mildner, guilliams, and yona discuss how the advent of new technologies such as fatemapping and singlecell analysis have revised our thinking on monocyte origin and function. Monocyte and macrophage imaging may rely on nanoparticles that are takenup by these cells and that can be detected noninvasively. Clinical significance of monocyte heterogeneity clinical. Blood monocyte subpopulations also express phenotypic differences that reflect heterogeneity associated with their origin, maturation and activation 18, 21, 22. Blood monocytes are precursors of dendritic cells, macrophages, and osteoclasts. As primary mediators of an organisms innate immunity, monocytes, and macrophages. Importantly, monocytes recruited during inflammation are often functionally distinct from resident macrophages or conventional dendritic cells. Cardiac monocytes and macrophages after myocardial. Macrophage heterogeneity in tissues wiley online library.
Reflecting their ancient evolutionary origin, macrophage. Request pdf monocyte and macrophage heterogeneity in the heart monocytes and macrophages are innate immune cells that reside and accumulate in the healthy and injured heart. The discovery of the heterogeneity of the monocyte and macrophage populations caused new studies of the structure and functions of these cells 20, 24 252627. B by 6 weeks, inflammatory cell infiltration at the infarct site has returned to baseline. We initiated the i like home study to examine monocyte heterogeneity in obesity and subclinical atherosclerosis. Clinical significance of monocyte heterogeneity pdf.
Developmental and functional heterogeneity of monocytes. Monocytosis is the state of excess monocytes in the peripheral blood. Over the past two decades, considerable attention to monocyte. Jun 07, 20 finally, from a perspective of monocyte and macrophage heterogeneity, precise lineage relationships between these cells and their subsets have yet to be determined in the steady state as well as in the diseased heart. Identification of a growing number of functionally different subsets of cells within populations of monocytederived immune cells has recently put monocyte heterogeneity into sharp focus. Here we outline emerging concepts in monocyte heterogeneity, emergency monopoiesis, and trained immunity and discuss how these bring new perspectives to monocyte research. In contrast, monocytederived macrophages that engraft into macrophage pools during inflammation show distinct gene signatures and often fail. Monocytes and macrophages are innate immune cells that reside and accumulate in the healthy and injured heart. The nature of monocytemacrophage heterogeneity is also difficult to assess due to the considerable plasticity of macrophages, their repertoire of receptors and extensive biosynthetic capacity. Multiple lines of evidence now point to the participation of innate and adaptive immunity and inflammatory signaling in a variety of cardiovascular conditions. Recently, they have also been shown to play a pivotal role in obesity. Colony stimulating factors and macrophage heterogeneity john a. Consequences for monocytederived immune cells sarasprangers, 1 vries, 2 andvincenteverts 1 department of oral cell biology and functional anatomy, academic centre for dentistry amsterdam acta. Advances in technology and genetic manipulation have permitted the dissection of the monocyte macrophage system in a way not previously imagined.
What is the evidence that discoveries in the mouse translate to patients with myocardial infarction. In this context, they outline emerging concepts in monocyte heterogeneity, emergency monopoiesis, and trained immunity, and discuss new perspectives in monocyte research. We should also explore how our current therapeutics interfere with monocyte and macrophage function. Peritoneal macrophage heterogeneity is associated with. However, as we discuss here, recent studies have shown that. Thus, in order to increase our understanding of macrophage differentiation and heterogeneity in human disease, we need to make use of models working with human macrophages. Pdf clinical significance of monocyte heterogeneity. Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Monocyte activation and differentiation towards distinct macrophage subpopulations m1 or m2 hinges on the predominant pro or antiinflammatory microenvironment within the lesion. Advances in technology and genetic manipulation have permitted the dissection of the monocytemacrophage system in a way not previously imagined. Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. Heterogeneous expression of apolipoproteine by human macrophages. Monocyte and macrophage heterogeneity semantic scholar. Macrophage heterogeneity and acute inflammation liddiard.
Identification of a growing number of functionally different subsets of cells within populations of monocyte derived immune cells has recently put monocyte heterogeneity into sharp focus. Brian k stansfield 0 1 david a ingram 0 vascular biology center, georgia regents university, augusta, georgia 1 department of pediatrics and neonatalperinatal medicine, georgia regents university, augusta, georgia monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. By interacting with epithelial, stromal and immune cells in the lung, they maintain alveolar integrity and orchestrate responses to. We also revisit the existing mirnome data to propose a canonical signature for each subset. During malignancy, tissue macrophages play an important role in promoting the survival, growth and spread of tumour cells 3. A large number of clinical studies support concepts of cardiac monocyte and macrophage heterogeneity recently described in mice. So far, there is little knowledge on macrophage heterogeneity in gca. The study of monocyte and macrophage heterogeneity has recently passed through a somewhat exciting period of research activity 1, 2. Hence, interest has burgeoned in this intersection. Myocardial monocyte and macrophage populations after ami. Using singlecell rna sequencing in a mouse model of sonic hedgehog medulloblastoma and analysis of bulk rna sequencing of human medulloblastoma, we investigated macrophage heterogeneity. They are a heterogeneous cell population with differences in size, phenotype. Here, we give an overview of the stateoftheart research regarding mirnas that are differentially expressed between monocyte subsets and how they influence monocyte functional heterogeneity in health and disease, with descriptions of specific mirnas.
Monocyte and macrophage heterogeneity in giant cell arteritis and polymyalgia rheumatica. After birth, bone marrowderived blood monocytes replenish resident macrophage populations with high turnover, such as gut. Therefore, we here describe a model of human primary macrophage generation that is easy to use and allows study of human monocytederived macrophages in vitro under various. Monocyte and macrophage heterogeneity in the heart. Here we examined apoe expression in human thp1 macrophages and monocytederived macrophages mdm. A monocyte count is part of a complete blood count and is expressed either as a percentage of monocytes among all white blood cells or as absolute numbers. Regulation of monocyte functional heterogeneity by mir146a. Human monocytederived macrophages are heterogenous. Monocyte and macrophage heterogeneity siamon gordon and philip r. Monocyte migration and widespread tissue distribution provide portals for microbial dissemination, as well as host protection. We hypothesized different spatial identities of macrophages, governed by local expression. The heterogeneity of lung macrophages in the susceptibility to disease luisa moralesnebreda1, alexander v. Until recently, human monocytes were subdivided based on expression of the surface marker cd16. Origin of monocytes and macrophages in a committed.
Jci insight singlecell analysis of fatemapped macrophages. The heterogeneity of lung macrophages in the susceptibility. The signals that induce the recruitment of circulating. The extensive heterogeneity of macrophage populations in vivo, revealed by population and single cell analysis, mandates exquisite selectivity to target particular subsets of infected cells, without collateral injury to the host, as emphasized by srivastava et al. Monocyte and macrophage heterogeneity in giant cell. Regulation of monocyte functional heterogeneity by mir. Both in humans and in mice, monocytetomacrophage differentiation involves global transcriptome changes that are tightly controlled by various transcriptional regulators and signaling mechanisms.
Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely. Monocyte subpopulations and or microenvironment 11 2. Singlecell transcriptomic profile reveals macrophage. Circulating monocytes give rise to mature macrophages and are also heterogeneous. Monocyte subpopulations andor microenvironment 11 2. Disease progression and regression are associated with different activation states of macrophages derived from inflammatory monocytes entering the plaques. They leave the circulation by squeezing through the blood vessel wall in a specialized process known as diapedesis, to give rise to heterogeneous tissue macrophages. After birth, bone marrowderived blood monocytes re.
Alveolar macrophages are specialised resident phagocytes in the alveolus, constituting the first line of immune cellular defence in the lung. The motivation behind the questions above is the need for new treatment concepts in heart failure. Functional macrophage heterogeneity in a mouse model of. Monocyte and macrophage heterogeneity in the heart request pdf. Proteomic profile of different phenotypes, abstract tissue macrophages play a key role in many aspects of human physiology and pathology.
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