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. Jun 21, 2010 recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. 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. Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Distinct monocyte populations give rise to dc 111, activated 111 and fibrogenic 18 macrophages gordon and pluddemann bmc biology 2017 15. Clinical significance of monocyte heterogeneity clinical. Although monocytes maintain several tissuespecific populations of immune cells in homeostasis, their contribution to populations of dendritic cells, macrophages, and osteoclasts is significantly. Frontiers understanding the heterogeneity of resident. 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.
Clinical significance of monocyte heterogeneity pdf paperity. Monocytederived macrophages mom can also acquire a kclike phenotype after inflammation. 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. Jci insight singlecell analysis of fatemapped macrophages. Monocyte derived macrophages mom can also acquire a kclike phenotype after inflammation. Review developmental and functional heterogeneity of monocytes. However, as we discuss here, recent studies have shown that. The existence of monocytes has been appreciated since at least the 1920s 5. For example, monocyte progenitor release from the bone marrow after coronary ligation in mice depends on. Hence, interest has burgeoned in this intersection. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop nichespecific functions. Though not dogmatic, general recognition that classical monocytes arise from the bone marrow and give rise to intermediate and. 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.
Monocyte subpopulations andor microenvironment 11 2. 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. Highresolution longitudinal n and oglycoprofiling of. This unit describes the isolation of monocytes from lymphocytes by adherence, gradient sedimentation on colloidal silica particles, and flow cytometry. Lu m, sarruf da, talukdar s, sharma s, li p, bandyopadhyay g. Sources of heterogeneity in human monocyte subsets laura j. Characterization of monocytemacrophage subsets in the skin. Monocytetomacrophage transition involves selective expression of serglycin, tsg6, hyaluronan, and versican and the formation of inter trypsin inhibitor and amyloidlike precursor protein complexes. 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. Monocytosis is the state of excess monocytes in the peripheral blood. Restricting promonocytes to the bone marrow, monocytes to the blood, and macrophages to the tissue precludes the existence of promonocytes. Recent accumulating evidence indicates a crucial involvement of macrophage lineage in the pathogenesis of systemic sclerosis ssc. 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. Human monocytederived macrophages are heterogenous.
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. A major characteristic of the model is that macrophage development follows a linear and spatiallyrestricted. Multiple lines of evidence now point to the participation of innate and adaptive immunity and inflammatory signaling in a variety of cardiovascular conditions. Monocyte migration into adipose tissue is induced by chemokines such as mcp1 also known as cc motif ligand 2 and regulated on activation normal. 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. A subpopulation of hladrbearing macrophages required for antigeninduced t cell activation also contains stimulators for autologousreactive t cells. Monocytetomacrophage differentiation is accompanied by changes in proteoglycan synthesis. Gene expression profiling reveals the defining features of. 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. Monocyte and macrophage heterogeneity semantic scholar. The effects of heterogeneous macrophage populations on their local tissue. 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.
Recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. Breast cancer is one of the most lifethreatening cancers. 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. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during. Furthermore, the plaque microenvironment offers polarisation. Monocytes are highly plastic and heterogeneous, and change their functional phenotype in response to environmental stimulation. Inflammation triggers the differentiation of ly6c hi monocytes into microbicidal macrophages or monocyte derived dendritic cells modcs. Only a few decades ago, students of the pathophysiology of cardiovascular disease paid little heed to the involvement of inflammation and immunity. Clinical significance of monocyte heterogeneity pdf. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. Pdf monocytes and macrophages have crucial and distinct roles in tissue. We should also explore how our current therapeutics interfere with monocyte and macrophage function.
Monocytes can differentiate into inflammatory or anti. 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%. Proteomic profile of different phenotypes, abstract tissue macrophages play a key role in many aspects of human physiology and pathology. 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. 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.
Herein, labelfree pgclcmsms was employed to profile with high resolution the n and oglycome associated with human monocyte to macrophage transition. 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. 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. 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. The present study investigated the patterns of monocyte. Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. M1 macrophages result from classic monocyte activation in response to proinflammatory stimuli, such as ifn. In analogy to murine studies, we hypothesized that. Granulocyte macrophage colonystimulating factor csf and macrophage csfdependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities. The heterogeneity of ly6chi monocytes controls their. 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.
The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. 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. Herein, labelfree pgclcmsms was employed to profile with high resolution the n and oglycome associated with human monocytetomacrophage transition. Origin of monocytes and macrophages in a committed.
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. Innate inflammation is a hallmark of both experimental and human atherosclerosis. Macrophage heterogeneity in atherosclerosis regression hstalks. National institute of dental researchnih, bethesda, maryland. Supplemental experimental procedures and figures s1s7. Over the past two decades, considerable attention to monocyte. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. Blood monocytes are precursors of dendritic cells, macrophages, and osteoclasts. The enormous heterogeneity in human monocyte size, morphology, phagocytic function and cell adhesion was first described in 1989 and was quickly. 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.
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. Frontiers understanding the heterogeneity of resident liver. These include fulllength papers on original research, rapid communications of new discoveries, letters, commentaries. However, the subsequent identifica tion of differential expression of antigenic markers showed that monocytes in human peripheral blood are hetero geneous. 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. Monocytes and macrophages express a wide range of sur. Highresolution longitudinal n and oglycoprofiling of human. Monocyte and macrophage heterogeneity in the heart circulation. Jun 07, 20 the motivation behind the questions above is the need for new treatment concepts in heart failure. Evidence from murine and human studies has suggested that monocytosis can be an indicator of various inflammatory diseases. Monocytes contribute to osteoclast multinucleation and also generate functional dendritic cells upon culture in gmcsf, with or without il4. Monocytes express various receptors, which monitor and sense environmental changes. Monocytes are attracted to a damaged site by chemical substances through chemotaxis, triggered by a range of stimuli including damaged cells, pathogens and. Macrophage heterogeneity and tissue lipids siamon gordon sir william dunn school of pathology, university of oxford, oxford, united kingdom.
In contrast, monocytederived macrophages that engraft into macrophage pools during inflammation show distinct gene signatures and often fail. Much of what is known about human monocyte heterogeneity is based on 2 subsets subdivided according to cd14 and cd16 expression. A major characteristic of the model is that 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. Not long ago, monocyte heterogeneity, monocyte heterogeneity was established in a murine model, 18 enabling researchers to study monocyte subsets in models of atherosclerosis. The liver is populated by different macrophage populations. In two recent publications, a specific contribution of certain monocyte subsets to atherogenesis was confirmed. The predominant innate immune cell in the atherosclerotic plaque is the monocytemacrophage. View the article pdf and any associated supplements and figures for a period of 48 hours. Blood monocyte subpopulations also express phenotypic differences that reflect heterogeneity associated with their origin, maturation and activation 18, 21, 22. 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.
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. Pdf link pdf citation r andreesen, kj bross, j osterholz, f emmrich. Isolation of monocytemacrophage populations wahl 1995. Macrophage heterogeneity is the main feature of the tumour microenvironment.
Monocyte activation and differentiation towards distinct macrophage subpopulations m1 or m2 hinges on the predominant pro or antiinflammatory microenvironment within the lesion. 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. Gels were loaded with 40,000 dpmlane and evaluated by phosphorimage analysis. Agedependent alterations of monocyte subsets and monocyte. Edward fisher on macrophage heterogeneity in atherosclerosis regression, part of a collection of online lectures. Sources of heterogeneity in human monocyte subsets. If you have not installed and configured the adobe acrobat reader on your system. Macrophages are present as resident cells in adipose pocytestissue, and blood monocytes are recruited in increased numbers to. Monocyte and macrophage heterogeneity in the heart. Macrophage heterogeneity in renal inflammation article pdf available in nephrology dialysis transplantation 1810. Macrophage heterogeneity in atherosclerosis regression video file. The present study investigated the patterns of monocyte differentiation and macrophage polarization in breast cancer.
Synovial fluid monocytemacrophage subsets and their. Fetal macrophages macrophage heterogeneity in human fetal tissue. Rather than distinct subsets, the monocyte gate consists a spectrum of progressively changing phenotypic markers. They are a heterogeneous cell population with differences in size, phenotype, and function. Both may be useful but these cells became valid diagnostic tools only when monocyte subsets are determined. The ontogenic heterogeneity of tissue macrophage is fascinating, and raises the. Macrophage heterogeneity in atherosclerosis regression. 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. Monocyte heterogeneity in obesity and subclinical atherosclerosis. Granulocytemacrophage colonystimulating factor csf and macrophage csfdependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities. Macrophage differentiation is accompanied by expression of unique extracellular matrix molecules.