Blood monocytes are precursors of dendritic cells, macrophages, and osteoclasts. Herein, labelfree pgclcmsms was employed to profile with high resolution the n and oglycome associated with human monocytetomacrophage transition. Gene expression profiling reveals the defining features of. Macrophage heterogeneity in atherosclerosis regression. Proteomic profile of different phenotypes, abstract tissue macrophages play a key role in many aspects of human physiology and pathology. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during. Finally, in response to macrophage colony stimulating factor mcsf, intermediate monocytes are initially expanded in the peripheral blood followed by a delayed increase in nonclassical monocyte frequency 24,32,33. Recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. Blood monocyte subpopulations also express phenotypic differences that reflect heterogeneity associated with their origin, maturation and activation 18, 21, 22. Over the past two decades, considerable attention to monocyte. Innate inflammation is a hallmark of both experimental and human atherosclerosis. Origin of monocytes and macrophages in a committed. Monocytes and macrophages express a wide range of sur. Restricting promonocytes to the bone marrow, monocytes to the blood, and macrophages to the tissue precludes the existence of promonocytes.
Hence, interest has burgeoned in this intersection. Monocytes are highly plastic and heterogeneous, and change their functional phenotype in response to environmental stimulation. The existence of monocytes has been appreciated since at least the 1920s 5. If you have not installed and configured the adobe acrobat reader on your system. Review developmental and functional heterogeneity of monocytes.
Characterization of monocytemacrophage subsets in the skin. The liver is populated by different macrophage populations. Only a few decades ago, students of the pathophysiology of cardiovascular disease paid little heed to the involvement of inflammation and immunity. 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. In contrast, monocytederived macrophages that engraft into macrophage pools during inflammation show distinct gene signatures and often fail. Monocyte heterogeneity in obesity and subclinical atherosclerosis. Macrophage heterogeneity in atherosclerosis regression video file. Clinical significance of monocyte heterogeneity pdf. However, macrophage polarization patterns in different tumour stages and the importance of its relationship to human epidermal growth factor receptor 2 her2 in breast cancer remains highly unclear. Monocyte activation and differentiation towards distinct macrophage subpopulations m1 or m2 hinges on the predominant pro or antiinflammatory microenvironment within the lesion. Frontiers understanding the heterogeneity of resident liver. Both may be useful but these cells became valid diagnostic tools only when monocyte subsets are determined. Highresolution longitudinal n and oglycoprofiling of.
However, as we discuss here, recent studies have shown that. However, the subsequent identifica tion of differential expression of antigenic markers showed that monocytes in human peripheral blood are hetero geneous. From the larger cohort of 62 africans we analyzed the five monocyte groupings with respect to changes in their surface expression of the phenotypic markers ccr2 and cx3cr1, and the mhc receptor hladr. In two recent publications, a specific contribution of certain monocyte subsets to atherogenesis was confirmed. Clinical significance of monocyte heterogeneity clinical. To analyze the assembly of the monocyte macrophage population, we evaluated the expression of cd163 and cd204 and various activated macrophage markers, in the inflammatory cells of the skin and in the peripheral blood mononuclear cells pbmcs derived from. Macrophage differentiation is accompanied by expression of unique extracellular matrix molecules. Monocytes can differentiate into inflammatory or anti. The present study investigated the patterns of monocyte. We should also explore how our current therapeutics interfere with monocyte and macrophage function. Human monocytederived macrophages are heterogenous. Edward fisher on macrophage heterogeneity in atherosclerosis regression, part of a collection of online lectures.
Although monocytes maintain several tissuespecific populations of immune cells in homeostasis, their contribution to populations of dendritic cells, macrophages, and osteoclasts is significantly. Jul 10, 20 only a few decades ago, students of the pathophysiology of cardiovascular disease paid little heed to the involvement of inflammation and immunity. 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. Highresolution longitudinal n and oglycoprofiling of human. Monocytes are derived from promonocytes in the bone marrow and circulate in the blood for about 24 hours before migrating to the tissues, such as the lung and liver, where they develop. This unit describes the isolation of monocytes from lymphocytes by adherence, gradient sedimentation on colloidal silica particles, and flow cytometry. Monocyte heterogeneity in cardiovascular disease springerlink. Herein, labelfree pgclcmsms was employed to profile with high resolution the n and oglycome associated with human monocyte to macrophage transition. Furthermore, the plaque microenvironment offers polarisation. Monocyte migration into adipose tissue is induced by chemokines such as mcp1 also known as cc motif ligand 2 and regulated on activation normal, t cell expressed and secreted rantes. Monocytes contribute to osteoclast multinucleation and also generate functional dendritic cells upon culture in gmcsf, with or without il4.
The present study investigated the patterns of monocyte differentiation and macrophage polarization in breast cancer. A subpopulation of hladrbearing macrophages required for antigeninduced t cell activation also contains stimulators for autologousreactive t cells. Clinical significance of monocyte heterogeneity pdf paperity. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. Multiple lines of evidence now point to the participation of innate and adaptive immunity and inflammatory signaling in a variety of cardiovascular conditions. Peripheral blood monocytes, which represent around 10% of circulating leukocytes in humans, are recognized as the largest pool of circulating progenitor cells and form a vital part of the immune system. Because the first two methods can result in cell activation induction of gene expression or protein secretion, and the third is technically difficult, a fourth protocol is presented which.
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. Sources of heterogeneity in human monocyte subsets laura j. For example, monocyte progenitor release from the bone marrow after coronary ligation in mice depends on. Rather than distinct subsets, the monocyte gate consists a spectrum of progressively changing phenotypic markers. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in your browser. Monocyte migration into adipose tissue is induced by chemokines such as mcp1 also known as cc motif ligand 2 and regulated on activation normal. Research article open access altered monocyte differentiation and macrophage polarization patterns in patients with breast cancer chihhsing hung1,2,3,4,5, fangming chen6,7,8, yiching lin1,9,10, meilan tsai1, shihling wang1, yenchun chen1,4, yiting chen1 and mingfeng hou7,8,11 abstract. Granulocyte macrophage colonystimulating factor csf and macrophage csfdependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities. To analyze the assembly of the monocytemacrophage population, we evaluated the expression of cd163 and cd204 and various activated macrophage markers, in the inflammatory cells of the skin and in the peripheral blood. Jun 07, 20 the motivation behind the questions above is the need for new treatment concepts in heart failure. Feb 14, 2015 finally, in response to macrophage colony stimulating factor mcsf, intermediate monocytes are initially expanded in the peripheral blood followed by a delayed increase in nonclassical monocyte frequency 24,32,33. 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. 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. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop nichespecific functions.
Monocytosis is the state of excess monocytes in the peripheral blood. 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. Monocyte subpopulations andor microenvironment 11 2. Gels were loaded with 40,000 dpmlane and evaluated by phosphorimage analysis. 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. Jci insight singlecell analysis of fatemapped macrophages. Macrophages are present as resident cells in adipose pocytestissue, and blood monocytes are recruited in increased numbers to. Evidence from murine and human studies has suggested that monocytosis can be an indicator of various inflammatory diseases. Lu m, sarruf da, talukdar s, sharma s, li p, bandyopadhyay g. Pdfs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%. Much of what is known about human monocyte heterogeneity is based on 2 subsets subdivided according to cd14 and cd16 expression.
Sources of heterogeneity in human monocyte subsets. Monocyte and macrophage heterogeneity in the heart circulation. A major characteristic of the model is that macrophage. Macrophage heterogeneity is the main feature of the tumour microenvironment. In analogy to murine studies, we hypothesized that. Agedependent alterations of monocyte subsets and monocyte. The most abundant one is composed by embryonicallyderived kupffer cells kc which reside in liver sinusoids and interact mainly with hsc and ec. Innate immunity and monocytemacrophage activation in. The ontogenic heterogeneity of tissue macrophage is fascinating, and raises the. However, macrophage polariz ation patterns in different tumour stages and the importance of its relationship to human epidermal growth factor receptor 2 her2 in breast cancer remains highly unclear. Macrophage heterogeneity in renal inflammation article pdf available in nephrology dialysis transplantation 1810. Frontiers understanding the heterogeneity of resident. Recent accumulating evidence indicates a crucial involvement of macrophage lineage in the pathogenesis of systemic sclerosis ssc. Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages.
A major characteristic of the model is that macrophage development follows a linear and spatiallyrestricted. M1 macrophages result from classic monocyte activation in response to proinflammatory stimuli, such as ifn. These include fulllength papers on original research, rapid communications of new discoveries, letters, commentaries. 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. Monocyte derived macrophages mom can also acquire a kclike phenotype after inflammation. 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. Clinical significance of monocyte heterogeneity, clinical and translational medicine, 2015, pp. 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. Monocyte and macrophage heterogeneity in the heart. National institute of dental researchnih, bethesda, maryland. Granulocytemacrophage colonystimulating factor csf and macrophage csfdependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities. 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. The enormous heterogeneity in human monocyte size, morphology, phagocytic function and cell adhesion was first described in 1989 and was quickly.
Breast cancer is one of the most lifethreatening cancers. The heterogeneity of ly6chi monocytes controls their. Macrophage heterogeneity in atherosclerosis regression hstalks. Not long ago, monocyte heterogeneity, monocyte heterogeneity was established in a murine model, 18 enabling researchers to study monocyte subsets in models of atherosclerosis. Altered monocyte differentiation and macrophage polarization. Characterization of monocytemacrophage subsets in the. Monocytetomacrophage differentiation is accompanied by changes in proteoglycan synthesis. In lesions in which the inflammatory stimulus is persistent, these ly6c high monocyte derived macrophages remain inflammatory by expressing il1. Jun 21, 2010 recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. When a monocyte enters damaged tissue through the endothelium of a blood vessel, a process known as leukocyte extravasation, it undergoes a series of changes to become a macrophage. 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. They are a heterogeneous cell population with differences in size, phenotype, and function.
View the article pdf and any associated supplements and figures for a period of 48 hours. The predominant innate immune cell in the atherosclerotic plaque is the monocytemacrophage. 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. Synovial fluid monocytemacrophage subsets and their. 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 semantic scholar. Inflammation triggers the differentiation of ly6c hi monocytes into microbicidal macrophages or monocyte derived dendritic cells modcs. Macrophage heterogeneity and tissue lipids siamon gordon sir william dunn school of pathology, university of oxford, oxford, united kingdom. Monocytes are attracted to a damaged site by chemical substances through chemotaxis, triggered by a range of stimuli including damaged cells, pathogens and. Supplemental experimental procedures and figures s1s7. Isolation of monocytemacrophage populations wahl 1995.
The contributions of lung macrophage and monocyte heterogeneity to influenza pathogenesis article in immunology and cell biology 953 september 2016 with 82 reads how we measure reads. Pdf link pdf citation r andreesen, kj bross, j osterholz, f emmrich. Pdf monocytes and macrophages have crucial and distinct roles in tissue. Monocytes express various receptors, which monitor and sense environmental changes. Monocytetomacrophage transition involves selective expression of serglycin, tsg6, hyaluronan, and versican and the formation of inter trypsin inhibitor and amyloidlike precursor protein complexes. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. 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.
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