After birth, bone marrowderived blood monocytes replenish resident macrophage populations with high turnover, such as gut. Phenotype, function, and differentiation potential of human. However, as we discuss here, recent studies have shown that. These macrophages then lead to the formation of scar tissue, which is characteristic to ipf. Monocyte and macrophage heterogeneity siamon gordon and philip r. Given the rapid progress in monocyte research from broad spectrum of inflammatory diseases, there is a need to summarize our knowledge in monocyte heterogeneity and its impact in human disease. Monocytosis is the state of excess monocytes in the peripheral blood.
So far, there is little knowledge on macrophage heterogeneity in gca. Monocyte and macrophage heterogeneity in the heart. The inner region of solid tumors is found to be highpressure, hypoxic, and immunosuppressive, providing a breeding ground for tumor aggressiveness and metastasis. M1 macrophages result from classic monocyte activation in response to proinflammatory stimuli, such as ifn.
Monocyte development, characterization and role in disease. Monocytes can differentiate into multiple progenies during inflammation. Monocytemacrophage disorders hematology in clinical. Role of monocytes in heart failure and atrial fibrillation. Here, we report the description and functional characterization of monocyte subsets. View the article pdf and any associated supplements and figures for a period of 48 hours. Results showed that human peritoneal macrophages are heterogeneous regarding their phenotype, cell complexity and functional abilities.
Agedependent alterations of monocyte subsets and monocyte. 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. The mature cells that comprise the monocytemacrophage system function both as phagocytes and as antigenpresenting cells. 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 lesions in which the inflammatory stimulus is persistent, these ly6c high monocyte derived macrophages remain inflammatory by expressing il1. Difference between monocyte and macrophage compare the. We therefore phenotyped monocytes from peripheral blood of healthy subjects. Monocyte development is regulated by sequential expression of key transcription factors in the following order. Lung macrophages stained with wrightgiemsa macrophages originate from blood monocytes that leave the circulation to differentiate in different tissues. Maxpar human monocytemacrophage phenotyping panel kit target. Phenotype of monocytederived tissue macrophages in selected pathologies. Both in humans and in mice, monocytetomacrophage differentiation involves global transcriptome changes that are tightly controlled by various transcriptional regulators and signaling mechanisms.
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. Macrophage differentiation is accompanied by expression of unique extracellular matrix molecules. Additionally new macrophage tracers could be designed to replace 18ffluorodeoxyglucose fdg as a more cell specific tracer in petct scans. To begin to explore whether tim4 and cd4 were markers of gut macrophage heterogeneity, we isolated the three subsets using facs for morphological and functional analyses fig. Monocyte differentiation and macrophage polarization. Reflecting their ancient evolutionary origin, macrophage. Nonmyeloid cells were removed by manual gating and visne analysis was performed on the remaining cells. However, the role of monocyte subset populations may be a logical explanation for the diversity in function. Clinical significance of monocyte heterogeneity springerlink.
Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Maxpar human monocytemacrophage phenotyping panel kit. Phenotype, function, and differentiation potential of. 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. Monitoring the intracellular phosphorylation of receptors adds one extra level of information on monocytemacrophage reaction that could be induced by any ligand such as cytokines or inflammatory products such as bacterial extracts or pams. Taken together, there are various mechanisms utilized by neutrophils and monocytes macrophages to regulate the clearance of cells in the resolution of inflammation. Raw data files dat and cel were gener ated in affymetrix.
Furthermore, it is important not to overinterpret the expression of a single marker, such as cd11c, as indicative of. Monocyte and macrophage plasticity in tissue repair and. Noninvasive leukocyte imaging answered questions regarding how monocyte and macrophage content in the infarct influences left ventricular remodeling and the evolution of heart failure. Circulating monocytes give rise to mature macrophages and are also heterogeneous. The main difference between monocyte and macrophage is that monocyte is the precursors of some of the macrophages whereas macrophages are the professional phagocytes, which engulf pathogens invading the body monocyte and macrophage are two types of cells found in the immune system of organisms. Origins and phenotypic heterogeneity of macrophages in. The motivation behind the questions is the need for new treatment concepts in heart failure. Until recently, human monocytes were subdivided based on expression of the surface marker cd16. Monocyte and macrophage heterogeneity semantic scholar. Tissue damage sensing is probably crucial at the second level of macrophage response, regardless of whether the damage is of a microbial nature. 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. Monocyte subpopulations and or microenvironment 11 2. Documentation of normal function and variation in this complement of subtypes, particularly their differentiation potential to dendritic cells dc or macrophages, remains incomplete.
Maxpar human monocytemacrophage phenotyping panel kit prd02017 v3 product information sheet pbmcs were stained with the maxpar human monocytemacrophage phenotyping panel kit. Monocyte and macrophage heterogeneity in the heart ncbi. These were the cells that remained morphologically closer to monocytes. Intermediate stages in monocytemacrophage differentiation. Proteomic profile of different phenotypes, abstract tissue macrophages play a key role in many aspects of human physiology and pathology. Both may be useful but these cells became valid diagnostic tools only when monocyte subsets are determined. Senescent monocytes and macrophages themselves undergo apoptosis and are cleared away by scavengers poon et al. We hypothesized different spatial identities of macrophages, governed by local expression. The ontogeny of monocyte subsets immunology frontiers.
Monocytetomacrophage transition involves selective expression of serglycin, tsg6, hyaluronan, and versican and the formation of inter. Macrophages and their precursors monocytes play a key role in inflammation and chronic inflammatory disorders. We should also explore how our current therapeutics interfere with monocyte and macrophage function. In contrast to mouse cmops, human cmops express cd5, a cytokine receptor and early hematopoieticmarker. Monocytetomacrophage differentiation and activation programs are accompanied by significant epigenetic remodeling where dna methylation associates with cell identity. Significant heterogeneity exists in the monocytemacrophage phenotype, which has been investigated functionally, morphologically, through cell surface markers, and more recently through genetically altered mouse models. 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. Blood monocyte subpopulations also express phenotypic differences that reflect heterogeneity associated with their origin, maturation and activation 18, 21, 22. We therefore phenotyped monocytes from peripheral blood of. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. The role of the various monocyte types in athero thrombotic. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely.
Here, we summarize recent findings in monocyte heterogeneity and their differentiation into dendritic cells, macrophages, and osteoclasts. Pdf macrophages are present in all vertebrate tissues, from midgestation throughout life. 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. Monocyte and macrophage heterogeneity researchgate. The heterogeneity of ly6chi monocytes controls their. Gels were loaded with 40,000 dpmlane and evaluated by phosphorimage analysis. The heterogeneity of the monocyte macrophage population may be explained by several alternatives. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during.
Human monocyte heterogeneity as revealed by highdimensional. Colony stimulating factors and macrophage heterogeneity. Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. In this study, we first examined monocyte heterogeneity in peripheral blood of healthy human subjects using mass cytometry and subsequent computational data analysis.
Download premium images you cant get anywhere else. There is a substantial heterogeneity among each macrophage population, which most probably reflects the required level of specialisation within the environment of any given tissue. Overall, it is thought that monocytes, which circulate in the blood, enter the lung tissue and become macrophages. Jun 21, 2010 recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. Human tumorassociated monocytesmacrophages and their. 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. Monocyte activation and differentiation towards distinct macrophage subpopulations m1 or m2 hinges on the predominant pro or antiinflammatory microenvironment within the lesion. Isolation of monocytemacrophage populations wahl 1995.
Trailexpressing monocytemacrophages are critical for. Human monocytederived macrophages are heterogenous. During malignancy, tissue macrophages play an important role in promoting the survival, growth and spread of tumour cells 3. Tissueresident macrophages in the intestine are long lived. Flow cytometry analysis of human peritoneal monocytemacrophage subsets based on the cd14cd16 expression pattern and forwardside scattering compared to blood. Characterization of monocyte subsets in human and mouse 4.
Human monocyte subsets have typically been defined using only cd14 and cd16 as surface markers. We initiated the i like home study to examine monocyte heterogeneity in obesity and subclinical atherosclerosis. Aug 24, 2018 flow cytometry analysis of human peritoneal monocyte macrophage subsets based on the cd14cd16 expression pattern and forwardside scattering compared to blood. The mononuclear phagocyte system, derived from the bone marrow progenitor cells, is primarily composed of monocytes, macrophages, and dendritic cells. Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. Monocytes express various receptors, which monitor and sense environmental changes. National institute of dental researchnih, bethesda, maryland. Monocytes can differentiate into inflammatory or anti. Publishers pdf, also known as version of record publication date.
Monocyte subpopulations andor microenvironment 11 2. 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. Monocytes are mononuclear leukocytes that circulate in the blood and differentiate into macrophages and dcs dendritic cells. Monocyte macrophage macrophage dendritic cell progenitor bone marrow blood spleen destination. Upon tissue damage or infection, monocytes are rapidly recruited to the tissue, where they can differentiate into tissue macrophages or dendritic cells. Human monocytetomacrophage differentiation involves. Evidence from murine and human studies has suggested that monocytosis can be an indicator of various inflammatory diseases.
Heterogeneity and pliability of tumoreducated macrophages. Ykl40 is a macrophagederived factor that serves as a wellknown serum marker of. Monocytetomacrophage differentiation is accompanied by changes in proteoglycan synthesis. Macrophage plasticity in response to gmcsf and csf1. 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. Jun 07, 20 noninvasive leukocyte imaging answered questions regarding how monocyte and macrophage content in the infarct influences left ventricular remodeling and the evolution of heart failure.
Monocytes are highly plastic and heterogeneous, and change their functional phenotype in response to environmental stimulation. University of groningen monocyte and macrophage heterogeneity. An initial level of macrophage activation occurs when early warning signals trigger monocyte recruitment and in situ activation or when il 4 induces in situ macrophage proliferation24. Monocyte macrophage macrophage dendritic cell progenitor bone marrow blood spleen destination tissue facs bone marrow 18fflt pet. The key difference between monocyte and macrophage is that monocyte is the largest type of white blood cell that can differentiate into macrophages or dendritic cells while macrophage is a large specialized white blood cell that engulfs infectious particles and cleans micro debris the immune system has different types of cells including lymphocytes, macrophages, monocytes, neutrophils, and. Monocytes are a group of cells circulating in the blood, bone marrow, and spleen, and constituting. There is also emerging evidence suggesting that neutro. Over the past two decades, considerable attention to monocyte. The hypothesis of monocyte subset heterogeneity and function in mi is formed on the basis of their role in modulating chemokine expression in mice, which, in turn, recruit ly6chigh and ly6clow monocyte subset. Interestingly, in 2003, an obesityassociated macrophage accumulation in adipose tissue has been described in mice.
Monocyte macrophage heterogeneity in myocardial infarction. Find highquality monocyte stock photos and editorial news pictures from getty images. Monocyte migration and widespread tissue distribution provide portals for microbial dissemination, as well as host protection. 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. Characterization of human peritoneal monocytemacrophage. 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. Here we show that dna methylation changes characteristic for monocytetomacrophage. Monocyte and macrophage heterogeneity in giant cell arteritis and polymyalgia. Colony stimulating factors and macrophage heterogeneity john a. The idea that monocytes derive from bone marrow precursors, circulate, and give rise to tissue macrophages was consolidated in the 1960s and has dominated. As gca is a systemic disease, we hypothesized that counts of monocyte subsets, as precursors of macrophages, were linked to expanded th1 and th17 cell counts in the blood.
Classical and nonclassical monocytes, and the macrophages and. Clinical significance of monocyte heterogeneity clinical. We believe that white blood cells called monocytes and macrophages play a key role in the development and progression of this disease. Edinburgh medical school thesis and dissertation collection.
For example, monocyte progenitor release from the bone marrow after coronary ligation in mice depends on. Monocyte and macrophage imaging may rely on nanoparticles that are taken up by these cells and that can be detected noninvasively. Monocyte subsets, their expression of tlr2 and tlr4 and the serum th1. Tissueresident macrophages in the intestine are long. The new technique is simplified, bringing real benefits in time and higher sensitivity. Hamilton arthritis and inflammation research centre, department of medicine, the university of melbourne.
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