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Journal of Leukocyte Biology Aug 2019Monocytes are innate immune cells of the mononuclear phagocyte system that have emerged as important regulators of cancer development and progression. Our understanding... (Review)
Review
Monocytes are innate immune cells of the mononuclear phagocyte system that have emerged as important regulators of cancer development and progression. Our understanding of monocytes has advanced from viewing these cells as a homogenous population to a heterogeneous system of cells that display diverse responses to different stimuli. During cancer, different monocyte subsets perform functions that contribute to both pro- and antitumoral immunity, including phagocytosis, secretion of tumoricidal mediators, promotion of angiogenesis, remodeling of the extracellular matrix, recruitment of lymphocytes, and differentiation into tumor-associated macrophages and dendritic cells. The ability of cancer to evade immune recognition and clearance requires protumoral signals to outweigh ongoing attempts by the host immune system to prevent tumor growth. This review discusses current understanding of monocyte heterogeneity during homeostasis, highlights monocyte functions in cancer progression, and describes monocyte-targeted therapeutic strategies for cancer treatment.
Topics: Animals; Biomarkers; Cell Movement; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Immunophenotyping; Monocytes; Neoplasms; Tumor Microenvironment
PubMed: 30776148
DOI: 10.1002/JLB.4RI0818-311R -
Frontiers in Immunology 2019Circulating monocytes can infiltrate mucosal or inflamed tissues where they differentiate into either macrophages or dendritic cells. This paradigm is supported by... (Review)
Review
Circulating monocytes can infiltrate mucosal or inflamed tissues where they differentiate into either macrophages or dendritic cells. This paradigm is supported by numerous studies conducted in mice and in different settings for human cells. Determining whether it holds true in humans is essential for the successful design of monocyte-targeting therapies. Despite limitations inherent to working with human samples, there is accumulating evidence of the existence of generated monocyte-derived cells in humans. Here, we review recent studies showing the recruitment of human monocytes into tissues and their differentiation into macrophages or dendritic cells, in normal or pathological settings. We examine the methods available in human studies to demonstrate the monocytic origin of infiltrating cells. Finally, we review the functions of human monocyte-derived cells and how they might contribute to pathogeny.
Topics: Animals; Dendritic Cells; Humans; Macrophages; Monocytes; Myelopoiesis
PubMed: 31456804
DOI: 10.3389/fimmu.2019.01907 -
Scandinavian Journal of Immunology Jul 2020Monocytes are important cells of the innate system. They are a heterogeneous type of cells consisting of phenotypically and functionally distinct subpopulations, which... (Review)
Review
Monocytes are important cells of the innate system. They are a heterogeneous type of cells consisting of phenotypically and functionally distinct subpopulations, which play a specific role in the control, development and escalation of the immunological processes. Based on the expression of superficial CD14 and CD16 in flow cytometry, they can be divided into three subsets: classical, intermediate and non-classical. Variation in the levels of human monocyte subsets in the blood can be observed in patients in numerous pathological states, such as infections, cardiovascular and inflammatory diseases, cancer and autoimmune diseases. The aim of this review is to summarize current knowledge of human monocyte subsets and their significance in homeostasis and in pathological conditions.
Topics: Colony-Stimulating Factors; Humans; Immunity, Innate; Macrophages; Monocytes; Receptors, Cell Surface
PubMed: 32243617
DOI: 10.1111/sji.12883 -
PloS One Jan 2010Differentiated macrophages are the resident tissue phagocytes and sentinel cells of the innate immune response. The phenotype of mature tissue macrophages represents the...
Differentiated macrophages are the resident tissue phagocytes and sentinel cells of the innate immune response. The phenotype of mature tissue macrophages represents the composite of environmental and differentiation-dependent imprinting. Phorbol-12-myristate-13-acetate (PMA) and 1,25-dihydroxyvitamin D3 (VD(3)) are stimuli commonly used to induce macrophage differentiation in monocytic cell lines but the extent of differentiation in comparison to primary tissue macrophages is unclear. We have compared the phenotype of the promonocytic THP-1 cell line after various protocols of differentiation utilising VD(3) and PMA in comparison to primary human monocytes or monocyte-derived macrophages (MDM). Both stimuli induced changes in cell morphology indicative of differentiation but neither showed differentiation comparable to MDM. In contrast, PMA treatment followed by 5 days resting in culture without PMA (PMAr) increased cytoplasmic to nuclear ratio, increased mitochondrial and lysosomal numbers and altered differentiation-dependent cell surface markers in a pattern similar to MDM. Moreover, PMAr cells showed relative resistance to apoptotic stimuli and maintained levels of the differentiation-dependent anti-apoptotic protein Mcl-1 similar to MDM. PMAr cells retained a high phagocytic capacity for latex beads, and expressed a cytokine profile that resembled MDM in response to TLR ligands, in particular with marked TLR2 responses. Moreover, both MDM and PMAr retained marked plasticity to stimulus-directed polarization. These findings suggest a modified PMA differentiation protocol can enhance macrophage differentiation of THP-1 cells and identify increased numbers of mitochondria and lysosomes, resistance to apoptosis and the potency of TLR2 responses as important discriminators of the level of macrophage differentiation for transformed cells.
Topics: Biomarkers; Blotting, Western; Cell Differentiation; Cell Line; Cytokines; Humans; Lysosomes; Macrophages; Microscopy, Confocal; Mitochondria; Monocytes; Nitric Oxide; Phagocytosis; Tetradecanoylphorbol Acetate
PubMed: 20084270
DOI: 10.1371/journal.pone.0008668 -
PloS One 2020The monocyte-derived dendritic cells (moDCs) are a subset of dendritic cells widely used in immunological studies as a convenient and easy approach after isolation of...
The monocyte-derived dendritic cells (moDCs) are a subset of dendritic cells widely used in immunological studies as a convenient and easy approach after isolation of mononuclear cells directly from peripheral blood mononuclear cells (PBMC). Both the purification and cell culture of monocytes impact on the differentiation of monocytes into moDCs. The methodology to isolate and differentiate monocytes into moDCs is still controversial. We aimed to compare three different protocols for monocyte isolation from PBMC: 1) Cold-aggregation; 2) Percoll gradient; and 3) Magnetic beads cell-enrichment. Additionally we also compared four different monocyte differentiation and culture techniques: 1) Cell culture media; 2) Serum sources; 3) required GM-CSF and IL-4 concentrations; 4) Cell culture systems. We used flow cytometry analysis of light scattering and/or expression of pan surface markers, such as CD3, CD14 and CD209 to determine isolation/differentiation degree. Purified PBMC followed by two steps of cold aggregation, yielded cell viability around 95% with poor monocyte enrichment (monocytes increase vs. lymphocytes reduction was not statistically significant, p>0.05). Conversely, monocyte isolation from PBMC with discontinuous Percoll gradient generated around 50% cell viability. Albeit, we observed a significant reduction (p≤0.05) of lymphocytes contaminants. The magnetic beads cell-enrichment yield cell viability higher than 95%, as high as a significant lymphocyte depletion (p≤0.005) when compared to all other techniques employed. The moDCs showed better differentiation based on increased CD209 expression, but lower CD14 levels, when cells were cultured in RPMI medium plus 500IU/mL of both GM-CSF and IL-4 in a semi-adherent fashion. Serum sources showed no influence on the culture performance. In conclusion, the magnetic beads cell-enrichment showed superior cell viability, indicating that this approach is a better choice to isolate monocytes, and moDCs cultured afterwards in appropriate medium, serum, cytokines and culture system might influence the monocytes differentiation into moDC.
Topics: Antigens, CD; Cell Differentiation; Cell Separation; Cell Survival; Cells, Cultured; Dendritic Cells; Flow Cytometry; Fluorescence; Humans; Monocytes; Scattering, Radiation
PubMed: 32271804
DOI: 10.1371/journal.pone.0231132 -
Cytometry. Part B, Clinical Cytometry May 2017In April 2013, a symposium was organized to highlight different aspects of differentiation and activation of the monocyte-macrophage lineage as analyzed on the flow...
In April 2013, a symposium was organized to highlight different aspects of differentiation and activation of the monocyte-macrophage lineage as analyzed on the flow cytometer. Characterization of this lineage requires knowledge of the maturation process from their progenitors that are present in bone marrow up to the mature monocytic cells in peripheral blood, because each monocytic lineage cell with an aberrant phenotype refers to the corresponding maturation stage. A standardized quantitative analysis will facilitate the monitoring of the pathological processes and the clinical features, such as the outcome of treatment. However, changes in marker expression by variation in intensity, asynchronism, and lineage infidelity must be considered. The dynamics of normal marker expressions in early differentiation stages, e.g. molecules like HLA II, CD64 or CD14, give rise to a hypothesis on their possible role in monocyte ontogeny. Besides their usual role in tissue homeostasis, mature macrophages may also play a similar role in hematopoiesis. This meeting highlighted the large potential of flow cytometric tools available for monitoring of all these aspects in the monocytic and macrophage cell lineage. © 2015 International Clinical Cytometry Society.
Topics: Cell Differentiation; Cell Lineage; Flow Cytometry; Humans; Macrophages; Monocytes
PubMed: 26332381
DOI: 10.1002/cyto.b.21280 -
Journal of Neuroinflammation Dec 2022Both resident microglia and invading peripheral immune cells can respond to injury and degeneration in the central nervous system. However, after dead and dying neurons...
BACKGROUND
Both resident microglia and invading peripheral immune cells can respond to injury and degeneration in the central nervous system. However, after dead and dying neurons have been cleared and homeostasis is re-established, it is unknown whether resident immune cells fully resume normal functions and to what degree the peripheral immune cells take up residence.
METHODS
Using flow cytometry, in vivo retinal imaging, immunohistochemistry, and single-cell mRNA sequencing, we assess resident microglia and monocyte-derived macrophages in the retina during and after the loss of photoreceptors in the Arr1 mouse model of inducible degeneration.
RESULTS
We find that photoreceptor loss results in a small, sustained increase in mononuclear phagocytes and, after degeneration wanes, these cells re-establish a spatial mosaic reminiscent of healthy retinas. Transcriptomic analysis revealed the population remained unusually heterogeneous, with several subpopulations expressing gene patterns consistent with mildly activated phenotypes. Roughly a third of "new resident" cells expressed markers traditionally associated with both microglial and monocytic lineages, making their etiology ambiguous. Using an inducible Cre-based fluorescent lineage tracing paradigm to confirm the origins of new resident immune cells, we found approximately equal numbers of microglia and monocyte-derived macrophages after degeneration had subsided. In vivo retinal imaging and immunohistochemical analysis showed that both subpopulations remained functionally responsive to sites of local damage, though on average the monocyte-derived cells had less morphological complexity, expressed higher levels of MHCII, and had less migratory activity than the native resident population.
CONCLUSIONS
Monocytic cells that infiltrate the retina during degeneration differentiate into monocyte-derived macrophages that can remain in the retina long-term. These monocyte-derived macrophages adopt ramified morphologies and microglia-like gene expression. However, they remain distinguishable in morphology and gene expression from resident microglia and appear to differ functionally, showing less responsiveness to subsequent retinal injuries. These findings support the idea that persistent changes in the local immune population that occur in response to cell loss in aging and progressive retinal diseases may include the establishment of subpopulations of bone marrow-derived cells whose ability to respond to subsequent insults wanes over time.
Topics: Mice; Animals; Retinal Degeneration; Microglia; Macrophages; Retina; Monocytes
PubMed: 36510226
DOI: 10.1186/s12974-022-02652-2 -
Antioxidants & Redox Signaling Nov 2016Monocytes and macrophages are key players in tissue homeostasis and immune responses. Epigenetic processes tightly regulate cellular functioning in health and disease.... (Review)
Review
SIGNIFICANCE
Monocytes and macrophages are key players in tissue homeostasis and immune responses. Epigenetic processes tightly regulate cellular functioning in health and disease. Recent Advances: Recent technical developments have allowed detailed characterizations of the transcriptional circuitry underlying monocyte and macrophage regulation. Upon differentiation and activation, enhancers are selected by lineage-determining and signal-dependent transcription factors. Enhancers are shown to be very dynamic and activation of these enhancers underlies the differences in gene transcription between monocytes and macrophages and their subtypes.
CRITICAL ISSUES
It has been shown that epigenetic enzymes regulate the functioning of these cells and targeting of epigenetic enzymes has been proven to be a valuable tool to dampen inflammatory responses. We give a comprehensive overview of recent developments and understanding of the epigenetic pathways that control monocyte and macrophage function and of the epigenetic enzymes involved in monocyte and macrophage differentiation and activation.
FUTURE DIRECTIONS
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 inflammatory repertoire in disease. Antioxid. Redox Signal. 25, 758-774.
Topics: Animals; Cell Differentiation; Enhancer Elements, Genetic; Epigenesis, Genetic; Gene Expression Regulation, Enzymologic; Humans; Macrophage Activation; Macrophages; Monocytes
PubMed: 26983461
DOI: 10.1089/ars.2016.6695 -
Frontiers in Immunology 2019Blood monocytes develop in the bone marrow before being released into the peripheral circulation. The circulating monocyte pool is composed of multiple subsets, each... (Review)
Review
Blood monocytes develop in the bone marrow before being released into the peripheral circulation. The circulating monocyte pool is composed of multiple subsets, each with specialized functions. These cells are recruited to repopulate resident monocyte-derived cells in the periphery and also to sites of injury. Several extrinsic factors influence the function and quantity of monocytes in the blood. Here, we outline the impact of sex, ethnicity, age, sleep, diet, and exercise on monocyte subsets and their function, highlighting that steady state is not a single physiological condition. A clearer understanding of the relationship between these factors and the immune system may allow for improved therapeutic strategies.
Topics: Aging; Animals; Environment; Ethnicity; Exercise; Homeostasis; Humans; Inheritance Patterns; Leukopoiesis; Life Style; Monocytes; Sex Characteristics; Sleep
PubMed: 31787976
DOI: 10.3389/fimmu.2019.02581 -
BioMed Research International 2020The brain is the most important and complex organ in most living creatures which serves as the center of the nervous system. The function of human brain includes... (Review)
Review
The brain is the most important and complex organ in most living creatures which serves as the center of the nervous system. The function of human brain includes controlling of the motion of the body and different organs and maintaining basic homeostasis. The disorders of the brain caused by a variety of reasons often severely impact the patients' normal life or lead to death in extreme cases. Monocyte is an important immune cell which is often recruited to the brain in a number of brain disorders. However, the role of monocytes may not be simply described as beneficial or detrimental. It significantly depends on the disease models and the stages of disease progression. In this review, we summarized the current knowledge about the role of monocytes and monocyte-derived macrophages during several common brain disorders. Major focuses include ischemic stroke, Alzheimer's disease, multiple sclerosis, intracerebral hemorrhage, and insomnia. The recruitment, differentiation, and function of monocyte in these diseases are reviewed.
Topics: Animals; Brain Diseases; Cell Differentiation; Humans; Inflammation; Macrophages; Mice; Monocytes
PubMed: 32596397
DOI: 10.1155/2020/9396021