Interactions between activated endothelium and monocytes precede atherosclerotic plaques. As monocytes undergo differentiation in vitro, they start to express lineagerestricted antigens specific for differentiation stages beyond the blood monocyte level as detected by monoclonal antibodies of the max series. Monocytes can differentiate into multiple progenies during inflammation. Mononuclear phagocytes are crucial components of the innate host defense system. Many studies have documented heterogeneity among human monocytes, but it was the discovery and characterization of monocyte subsets in the mouse that enabled investigation into the relevance of monocyte heterogeneity in cardiovascular disease models. Distinct monocyte populations give rise to dc 111, activated 111 and fibrogenic 18 macrophages gordon and pluddemann bmc biology 2017 15. Monocyte and macrophage heterogeneity and tolllike receptors.
Frontiers understanding the heterogeneity of resident. Additionally, since these macrophage populations are present in both. Here, we studied the utility of macrophage derived factors and markers of angiogenesis. Macrophage heterogeneity in tissues wiley online library. Monocyte subpopulations and or microenvironment 11 2. The idea that monocytes derive from bone marrow precursors, circulate, and give rise to tissue macrophages was consolidated in the 1960s and has dominated. Terminal maturation of human macrophages is an important step for creation of cell diversity amongst sitespecific subpopulations and their functional competence in situ. Monocytes contribute to osteoclast multinucleation and also generate functional dendritic cells upon culture in gmcsf, with or without il4. Monocyte and macrophage heterogeneity in the heart.
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. Macrophages mac are important effector cells of the immune system. Macrophages are present as resident cells in adipose tissue, and blood monocytes are recruited in increased numbers to sites of lipid. University of groningen monocyte and macrophage heterogeneity. Epigenetic regulation of monocyte and macrophage function. Monocytes and macrophages are innate immune cells that reside and accumulate in. 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. In contrast to mouse cmops, human cmops express cd5, a cytokine receptor and early hematopoieticmarker. Blood monocytes are precursors of dendritic cells, macrophages, and osteoclasts.
Blood monocyte subpopulations also express phenotypic differences that reflect heterogeneity associated with their origin, maturation and activation 18, 21, 22. The ontogenic heterogeneity of tissue macrophage is fascinating, and raises the question of why it is that fetal. The inner region of solid tumors is found to be highpressure, hypoxic, and immunosuppressive, providing a breeding ground for tumor aggressiveness and metastasis. They arise from circulating blood monocytes mo, which undergo further maturation. A key challenge for the field today is to integrate the information derived from these novel investigations. The liver is populated by different macrophage populations. Gaps and future directions in understanding monocyte heterogeneity. The existence of monocytes has been appreciated since at least the 1920s. By interacting with epithelial, stromal and immune cells in the lung, they maintain alveolar integrity and orchestrate responses to environmental challenges. A major characteristic of the model is that macrophage development follows a linear and spatiallyrestricted. Although monocytes maintain several tissuespecific populations of immune cells in homeostasis, their contribution to populations of dendritic cells, macrophages, and osteoclasts is significantly increased in inflammation. Jci insight singlecell analysis of fatemapped macrophages.
Jan 17, 2018 efficiency of monocytetomacrophage differentiation is regulated by ppm1a. In the present study, the authors examined the functional heterogeneity of m. They are a heterogeneous cell population with differences in size, phenotype, and function. The interaction of ccl2ccr2 and cx3cl1cx3cr1 pair mediates egress of circulating monocytes and their recruitment into the ra synovium 6, 71, 97. Monocyte heterogeneity and function frontiers research topic. Monocyte derived macrophages represent the key cell type of the innate immune system. Pdf monocytes and macrophages have crucial and distinct roles in tissue homeostasis and immunity, but they. Ccl2monocyte chemoattractant protein1 regulates inflammatory responses critical to healing myocardial infarcts. 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. In lesions in which the inflammatory stimulus is persistent, these ly6c high monocyte derived macrophages remain inflammatory by expressing il1.
Monocytederived macrophages mom can also acquire a kclike phenotype after inflammation. The most abundant one is composed by embryonicallyderived kupffer cells kc which reside in liver sinusoids and interact mainly with hsc and ec. Here, we studied the utility of macrophagederived factors and markers of angiogenesis. As a consequence, monocyte and macrophage heterogeneity can be re. Alveolar macrophages are specialised resident phagocytes in the alveolus, constituting the first line of immune cellular defence in the lung. Myocardial monocyte and macrophage populations after ami. However, as we discuss here, recent studies have shown that. The idea that monocytes derive from bone marrow precursors, circulate, and give rise to tissue macrophages was consolidated in the 1960s and has dominated much of our thinking since 6. Singlecell analysis of fatemapped macrophages reveals heterogeneity, including stemlike properties, during atherosclerosis progression and regression jianda lin, 1 hitoo nishi, 2 jordan poles, 1 xiang niu, 4 caroline mccauley, 1 karishma rahman, 2 emily j.
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. For example, macrophage populations after ir have a temporally shifted immune response, with macrophage populations at the infarct site peaking 4 days earlier than in the permanent ligation model and having almost completely resolved by 7 days. Jan 12, 2006 however, the precise mechanism of the generation of macrophage heterogeneity is not known. Macrophage heterogeneity and acute inflammation liddiard. The phosphatase ppm1a controls monocytetomacrophage. Monocyte diversity in chronic inflammatory diseases. Monocyte heterogeneity in obesity and subclinical atherosclerosis. Monocyte and macrophage heterogeneity in the heart circulation. The heterogeneity of the monocyte macrophage population may be explained by several alternatives.
For example, monocyte progenitor release from the bone marrow after coronary ligation in mice depends on. Tsujioka h, imanishi t, ikejima h, et al impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial. Clinical significance of monocyte heterogeneity pdf. The mononuclear phagocyte system mps was originally proposed as a new classification of macrophages, blood monocytes, and their precursors, based upon criteria of morphology, function, origin, and kinetics 1, 2. The existence of monocytes has been appreciated since at least the 1920s 5. Siamon gordon emeritus professor, university of oxford, sir william dunn school of pathology, uk published on may 31, 2009 archived on october 16, 2017 73 min. 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. Monocyte and macrophage heterogeneity semantic scholar. Both in humans and in mice, monocyte to macrophage differentiation involves global transcriptome changes that are tightly controlled by various transcriptional regulators and signaling mechanisms. Gaps and future directions in understanding monocyte heterogeneity recent adherence to the tripartite description of monocytes based on expression of cd14 and cd16 along with standardized gating strategies has enabled investigators to more thoroughly explore the nature of monocyte differentiation and function in human disease.
Concomitantly, immunological imprinting of either tolerance immunosuppression or trained immunity innate immune memory determines the functional fate of monocytes and monocytederived macrophages, as observed after infection or vaccination. Cells such as macrophages and monocytes phagocytose and process pathogens, produce inflammatory mediators, and link the innate and the adaptive immune systems. 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. Cardiac monocytes and macrophages after myocardial infarction. Both may be useful but these cells became valid diagnostic tools only when monocyte subsets are determined. Macrophages definition of macrophages by the free dictionary. Monocyte derived macrophages mom can also acquire a kclike phenotype after inflammation. Thus, studying macrophage biology is essential for increasing our knowledge on the pathophysiology of many diseases and to allow development of novel therapies. Blood monocyte heterogeneity and markers of endothelial. Clinical significance of monocyte heterogeneity pdf paperity. Monocytederived macrophages represent the key cell type of the innate immune system. Monocyte development is regulated by sequential expression of key transcription factors in the following order. B by 6 weeks, inflammatory cell infiltration at the infarct site has returned to baseline, leaving an acellular collagen. They were maintained under specificpathogenfree conditions in.
Advanced characterization of monocyte heterogeneity and high dimensional approaches. Monocyte and macrophage heterogeneity in the heart ncbi. Frontiers understanding the heterogeneity of resident liver. The method involved embryoid body eb formation in hes media, directed differentiation with macrophage colonystimulating factor and interleukin il3, and harvest of nonadherent monocytes from the culture supernatants. The key challenges in the upcoming years will be to study epigenetic changes in human disease and to better understand how epigenetic pathways control the in. 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. In this context, they outline emerging concepts in monocyte heterogeneity, emergency monopoiesis, and trained immunity, and discuss new perspectives in monocyte research. 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. In two recent publications, a specific contribution of certain monocyte subsets to atherogenesis was confirmed. 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, university of amsterdam and vu university amsterdam, move research institute amsterdam, gustav mahlerlaan.
Monocytosis is the state of excess monocytes in the peripheral blood. Over the past two decades, considerable attention to monocyte. Furthermore, it is important not to overinterpret the expression of a single marker, such as cd11c, as indicative of. This may explain the heterogeneity character of monocyte subsets and their polarization into their own other subsets as per demand in the ra synovium. 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. Disorders of the monocytemacrophage lineage are quite heterogeneous and include benign disorders such as langerhanscell histiocytosis, reactive histiocytosis, and the lysosomal storage diseases, as well as monocytic and histiocytic malignant proliferations. They play an important role in many inflammatory diseases including atherosclerosis or cancer 2. Differentiation pathways of monocyte into steadystate tissue macrophages. Consequences for monocytederived immune cells article pdf available in journal of immunology research 20163. Furthermore, it is important not to overinterpret the expression of a single marker, such as cd11c, as indicative of dc differentiation. Recent adherence to the tripartite description of monocytes based on expression of cd14 and cd16 along with standardized gating strategies has enabled investigators to more thoroughly explore the nature of monocyte differentiation and function in human disease.
However, the precise mechanism of the generation of macrophage heterogeneity is not known. Clinical significance of monocyte heterogeneity brian k stansfield1,2,6 and david a ingram3,4,5 abstract monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. 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. As the monocyte enters the tissue and differentiates into a macrophage, the cell volume and number of cytoplasmic granules increase. Ppm1a monocytes were treated with a pma 100 ngml or b bryostatin 10 nm to induce. Ankylosing spondylitis as is associated with excessive cardiovascular cv morbidity. The concept was based upon many lines of evidence that in adult mice, resident tissue macrophage populations are. In the immune system, monocytes, macrophages gordon and taylor, 2005, bcells, and tcells show heterogeneity. Yeung, 1 nikollaq vozhilla, 1 ada weinstock, 2 stephen a. Efficiency of monocytetomacrophage differentiation is regulated by ppm1a. Macrophage ontogeny and the mononuclear phagocyte system. A large number of clinical studies support concepts of cardiac monocyte and macrophage heterogeneity recently described in mice. The transformed monocytemacrophage appears when clean up of the csf is necessary because of degenerating cells and debris, often due to a subarachnoid hemorrhage sah or meningitis.
Not long ago, monocyte heterogeneity, monocyte heterogeneity was established in a murine model, 18 enabling researchers to study monocyte subsets in models of atherosclerosis. Concomitantly, immunological imprinting of either tolerance immunosuppression or trained immunity innate immune memory determines the functional fate of monocytes and monocyte derived macrophages, as observed after infection or vaccination. 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. Developmental and functional heterogeneity of monocytes. Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. May 19, 2015 tissue macrophages play a crucial role in the maintenance of tissue homeostasis and also contribute to inflammatory and reparatory responses during pathogenic infection and tissue injury. The monocyte is a spherical cell with prominent surface ruffles and blebs when examined by scanning electron microscopy. Monocyte differentiation and macrophage polarization.
Because there are no accurate disease specific and prognostic biomarkers for gca and pmr, the second aim of this thesis was to translate knowledge on the immunopathology of gcapmr to the clinic. The mature cells that comprise the monocytemacrophage system function both as phagocytes and as antigenpresenting cells. A major characteristic of the model is that macrophage development follows a linear and spatially. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. Jun 07, 20 the motivation behind the questions above is the need for new treatment concepts in heart failure. Gels were loaded with 40,000 dpmlane and evaluated by phosphorimage analysis. The role of innate immune receptors such as tolllike receptors tlrs in the recognition of pathogens is critical for mounting a precise and targeted.
Tissue macrophages, monocytes, macrophages, heterogeneity, phenotype, markers. An in vitro model to study heterogeneity of human macrophage. Macrophage differentiation is accompanied by expression of unique extracellular matrix molecules. As an example, tcell heterogeneity is essential for an effective immune response. In this image, one monocyte and two macrophages are indicated by the arrows, although it is not necessary to report them as distinct cells. Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Monocyte subpopulations andor microenvironment 11 2. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop nichespecific functions. Our aim was to quantify blood monocyte subsets in relation to endothelial activation and inflammatory activity in subjects with as who were free of clinical atherosclerotic cv disease. We read with interest the new data from lescoat et al and their interesting comments concerning our research letter on the identification of circulating cells coexpressing m1 and m2 phenotype markers in patients affected by systemic sclerosis ssc compared with healthy subjects hss. The heterogeneity of lung macrophages in the susceptibility.
Cardiac monocytes and macrophages after myocardial. Monocytetomacrophage differentiation is accompanied by changes in proteoglycan synthesis. Structure, receptors, and functions of monocytes and. Clinical significance of monocyte heterogeneity clinical. The heterogeneity of ly6chi monocytes controls their. In the present study we summarize our data and other studies concerning the variability and instability in the expression of markers and functions by monocytes and macrophages as well as the analysis of cloned populations of macrophages.
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