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. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. 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. Over the past two decades, considerable attention to monocyte. 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. 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. The existence of monocytes has been appreciated since at least the 1920s 5.
Macrophage differentiation is accompanied by expression of unique extracellular matrix molecules. Rather than distinct subsets, the monocyte gate consists a spectrum of progressively changing phenotypic markers. Monocytes contribute to osteoclast multinucleation and also generate functional dendritic cells upon culture in gmcsf, with or without il4. 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. 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. Gene expression profiling reveals the defining features of. This unit describes the isolation of monocytes from lymphocytes by adherence, gradient sedimentation on colloidal silica particles, and flow cytometry. Highresolution longitudinal n and oglycoprofiling of human. Blood monocyte subpopulations also express phenotypic differences that reflect heterogeneity associated with their origin, maturation and activation 18, 21, 22. Monocytederived macrophages mom can also acquire a kclike phenotype after inflammation. 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.
Monocyte heterogeneity in cardiovascular disease springerlink. Gels were loaded with 40,000 dpmlane and evaluated by phosphorimage analysis. Pdf link pdf citation r andreesen, kj bross, j osterholz, f emmrich. 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.
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. In two recent publications, a specific contribution of certain monocyte subsets to atherogenesis was confirmed. Macrophage heterogeneity in atherosclerosis regression video file. 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. Lu m, sarruf da, talukdar s, sharma s, li p, bandyopadhyay g. Jci insight singlecell analysis of fatemapped macrophages. Only a few decades ago, students of the pathophysiology of cardiovascular disease paid little heed to the involvement of inflammation and immunity. Agedependent alterations of monocyte subsets and monocyte. 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. Altered monocyte differentiation and macrophage polarization. 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.
Macrophages are present as resident cells in adipose pocytestissue, and blood monocytes are recruited in increased numbers to. Isolation of monocytemacrophage populations wahl 1995. Frontiers understanding the heterogeneity of resident liver. Highresolution longitudinal n and oglycoprofiling of. In analogy to murine studies, we hypothesized that. 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.
The heterogeneity of ly6chi monocytes controls their. If you have not installed and configured the adobe acrobat reader on your system. 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. Monocyte activation and differentiation towards distinct macrophage subpopulations m1 or m2 hinges on the predominant pro or antiinflammatory microenvironment within the lesion. Monocyte derived macrophages mom can also acquire a kclike phenotype after inflammation. Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. 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. Not long ago, monocyte heterogeneity, monocyte heterogeneity was established in a murine model, 18 enabling researchers to study monocyte subsets in models of atherosclerosis. A major characteristic of the model is that macrophage. The ontogenic heterogeneity of tissue macrophage is fascinating, and raises the. Sources of heterogeneity in human monocyte subsets.
M1 macrophages result from classic monocyte activation in response to proinflammatory stimuli, such as ifn. Macrophage heterogeneity in atherosclerosis regression. The predominant innate immune cell in the atherosclerotic plaque is the monocytemacrophage. Monocytes and macrophages express a wide range of sur. The present study investigated the patterns of monocyte. Monocyte heterogeneity in obesity and subclinical atherosclerosis. Clinical significance of monocyte heterogeneity pdf paperity. Macrophage heterogeneity is the main feature of the tumour microenvironment. Macrophage heterogeneity and tissue lipids siamon gordon sir william dunn school of pathology, university of oxford, oxford, united kingdom. Monocyte and macrophage heterogeneity in the heart. View the article pdf and any associated supplements and figures for a period of 48 hours. 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. We should also explore how our current therapeutics interfere with monocyte and macrophage function.
Monocyte and macrophage heterogeneity in the heart circulation. These include fulllength papers on original research, rapid communications of new discoveries, letters, commentaries. Innate inflammation is a hallmark of both experimental and human atherosclerosis. Clinical significance of monocyte heterogeneity clinical. Distinct monocyte populations give rise to dc 111, activated 111 and fibrogenic 18 macrophages gordon and pluddemann bmc biology 2017 15. They are a heterogeneous cell population with differences in size, phenotype, and function. For example, monocyte progenitor release from the bone marrow after coronary ligation in mice depends on.
Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. Macrophage heterogeneity in atherosclerosis regression hstalks. Macrophages are present as resident cells in adipose pocytestissue, and blood monocytes are recruited in increased numbers to sites of lipid accumula. National institute of dental researchnih, bethesda, maryland. Monocytetomacrophage transition involves selective expression of serglycin, tsg6, hyaluronan, and versican and the formation of inter trypsin inhibitor and amyloidlike precursor protein complexes. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during. Monocyte subpopulations andor microenvironment 11 2. 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. In lesions in which the inflammatory stimulus is persistent, these ly6c high monocyte derived macrophages remain inflammatory by expressing il1. Monocytes are attracted to a damaged site by chemical substances through chemotaxis, triggered by a range of stimuli including damaged cells, pathogens and. 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%. In contrast, monocytederived macrophages that engraft into macrophage pools during inflammation show distinct gene signatures and often fail. The enormous heterogeneity in human monocyte size, morphology, phagocytic function and cell adhesion was first described in 1989 and was quickly. Frontiers understanding the heterogeneity of resident.
Inflammation triggers the differentiation of ly6c hi monocytes into microbicidal macrophages or monocyte derived dendritic cells modcs. 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. Human monocytederived macrophages are heterogenous. Proteomic profile of different phenotypes, abstract tissue macrophages play a key role in many aspects of human physiology and pathology. 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.
Monocytetomacrophage differentiation is accompanied by changes in proteoglycan synthesis. 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 semantic scholar. Sources of heterogeneity in human monocyte subsets laura j. 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. 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.
Characterization of monocytemacrophage subsets in the skin. Granulocytemacrophage colonystimulating factor csf and macrophage csfdependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities. Monocytosis is the state of excess monocytes in the peripheral blood. Review developmental and functional heterogeneity of monocytes. Jun 21, 2010 recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. Synovial fluid monocytemacrophage subsets and their. Chronic, lowgrade inflammation of the synovium synovitis is a hallmark of osteoarthritis oa, thus understanding of oa immunobiology, mediated by immune effectors, is of importance. 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. Pdf monocytes and macrophages have crucial and distinct roles in tissue. Breast cancer is one of the most lifethreatening cancers.
Hence, interest has burgeoned in this intersection. Innate immunity and monocytemacrophage activation in. Much of what is known about human monocyte heterogeneity is based on 2 subsets subdivided according to cd14 and cd16 expression. A subpopulation of hladrbearing macrophages required for antigeninduced t cell activation also contains stimulators for autologousreactive t cells. 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. 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. 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. Edward fisher on macrophage heterogeneity in atherosclerosis regression, part of a collection of online lectures. Macrophage heterogeneity in renal inflammation article pdf available in nephrology dialysis transplantation 1810. Journal of leukocyte biology considers manuscripts of original investigations focusing on the origins, developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes, and other cells involved in host defense. Recent accumulating evidence indicates a crucial involvement of macrophage lineage in the pathogenesis of systemic sclerosis ssc.
The liver is populated by different macrophage populations. Though not dogmatic, general recognition that classical monocytes arise from the bone marrow and give rise to intermediate and. Clinical significance of monocyte heterogeneity, clinical and translational medicine, 2015, pp. The effects of heterogeneous macrophage populations on their local tissue. Granulocyte macrophage colonystimulating factor csf and macrophage csfdependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities. Both may be useful but these cells became valid diagnostic tools only when monocyte subsets are determined. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. Origin of monocytes and macrophages in a committed. Evidence from murine and human studies has suggested that monocytosis can be an indicator of various inflammatory diseases. Multiple lines of evidence now point to the participation of innate and adaptive immunity and inflammatory signaling in a variety of cardiovascular conditions. 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.
Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. 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. 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. Restricting promonocytes to the bone marrow, monocytes to the blood, and macrophages to the tissue precludes the existence of promonocytes. Monocytes can differentiate into inflammatory or anti. Monocytes express various receptors, which monitor and sense environmental changes. Clinical significance of monocyte heterogeneity pdf. The most abundant one is composed by embryonicallyderived kupffer cells kc which reside in liver sinusoids and interact mainly with hsc and ec. Herein, labelfree pgclcmsms was employed to profile with high resolution the n and oglycome associated with human monocyte to macrophage transition. However, the subsequent identifica tion of differential expression of antigenic markers showed that monocytes in human peripheral blood are hetero geneous.
Supplemental experimental procedures and figures s1s7. 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. Although monocytes maintain several tissuespecific populations of immune cells in homeostasis, their contribution to populations of dendritic cells, macrophages, and osteoclasts is significantly. Recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. 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. The present study investigated the patterns of monocyte differentiation and macrophage polarization in breast cancer. A major characteristic of the model is that macrophage development follows a linear and spatiallyrestricted. However, as we discuss here, recent studies have shown that. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop nichespecific functions. Monocytes are highly plastic and heterogeneous, and change their functional phenotype in response to environmental stimulation. Characterization of monocytemacrophage subsets in the. Fetal macrophages macrophage heterogeneity in human fetal tissue. 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.
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