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Cellular Immunology 2014Myocardial infarction (MI), secondary to atherosclerotic plaque rupture and occlusive thrombi, triggers acute margination of inflammatory neutrophils and monocyte... (Review)
Review
Myocardial infarction (MI), secondary to atherosclerotic plaque rupture and occlusive thrombi, triggers acute margination of inflammatory neutrophils and monocyte phagocyte subsets to the damaged heart, the latter of which may give rise briefly to differentiated macrophage-like or dendritic-like cells. Within the injured myocardium, a primary function of these phagocytic cells is to remove damaged extracellular matrix, necrotic and apoptotic cardiac cells, as well as immune cells that turn over. Recognition of dying cellular targets by phagocytes triggers intracellular signaling, particularly in macrophages, wherein cytokines and lipid mediators are generated to promote inflammation resolution, fibrotic scarring, angiogenesis, and compensatory organ remodeling. These actions cooperate in an effort to preserve myocardial contractility and prevent heart failure. Immune cell function is modulated by local tissue factors that include secreted protease activity, oxidative stress during clinical reperfusion, and hypoxia. Importantly, experimental evidence suggests that monocyte function and phagocytosis efficiency is compromised in the setting of MI risk factors, including hyperlipidemia and ageing, however underlying mechanisms remain unclear. Herein we review seminal phagocyte and cardiac molecular factors that lead to, and culminate in, the recognition and removal of dying injured myocardium, the effects of hypoxia, and their relationship to cardiac infarct size and heart healing.
Topics: Animals; Cell Hypoxia; Humans; Inflammation; Mice; Myocardial Infarction; Myocytes, Cardiac; Phagocytes; Wound Healing
PubMed: 24862542
DOI: 10.1016/j.cellimm.2014.04.006 -
Current Biology : CB Jan 2021New work shows that the glycocalyx meshwork on the surface of macrophages prevents phagocytic receptors from binding their ligands by two means - electrostatic charge...
New work shows that the glycocalyx meshwork on the surface of macrophages prevents phagocytic receptors from binding their ligands by two means - electrostatic charge and steric hindrance. Components of this barrier are present on pathogenic and malignant targets that elude phagocytosis.
Topics: Glycocalyx; Ligands; Macrophages; Phagocytes; Phagocytosis
PubMed: 33434480
DOI: 10.1016/j.cub.2020.10.066 -
Immunity Mar 2016Phagocytes are crucial for host defense against bacterial pathogens. As first demonstrated by Metchnikoff, neutrophils and mononuclear phagocytes share the capacity to... (Review)
Review
Phagocytes are crucial for host defense against bacterial pathogens. As first demonstrated by Metchnikoff, neutrophils and mononuclear phagocytes share the capacity to engulf, kill, and digest microbial invaders. Generally, neutrophils focus on extracellular, and mononuclear phagocytes on intracellular, pathogens. Reciprocally, extracellular pathogens often capitalize on hindering phagocytosis and killing of phagocytes, whereas intracellular bacteria frequently allow their engulfment and then block intracellular killing. As foreseen by Metchnikoff, phagocytes become highly versatile by acquiring diverse phenotypes, but still retaining some plasticity. Further, phagocytes engage in active crosstalk with parenchymal and immune cells to promote adjunctive reactions, including inflammation, tissue healing, and remodeling. This dynamic network allows the host to cope with different types of microbial invaders. Here we present an update of molecular and cellular mechanisms underlying phagocyte functions in antibacterial defense. We focus on four exemplary bacteria ranging from an opportunistic extracellular to a persistent intracellular pathogen.
Topics: Animals; Bacteria; Bacterial Infections; Cell Differentiation; Extracellular Space; Host-Pathogen Interactions; Humans; Immunity, Cellular; Inflammation; Intracellular Space; Phagocytes; Phagocytosis; Regeneration; Wound Healing
PubMed: 26982355
DOI: 10.1016/j.immuni.2016.02.014 -
Nature Reviews. Immunology Jun 2012Phagocytosis - the process by which macrophages, dendritic cells and other myeloid phagocytes internalize diverse particulate targets - is a key mechanism of innate... (Review)
Review
Phagocytosis - the process by which macrophages, dendritic cells and other myeloid phagocytes internalize diverse particulate targets - is a key mechanism of innate immunity. The molecular and cellular events that underlie the binding of targets to a phagocyte and their engulfment into phagosomes have been extensively studied. More recent data suggest that the process of phagocytosis itself provides information to myeloid phagocytes about the nature of the targets they are engulfing and that this helps to tailor inflammatory responses. In this Review, we discuss how such information is acquired during phagocytosis and how it is processed to coordinate an immune response.
Topics: Animals; Humans; Immunity, Innate; Inflammasomes; Macrophages; Models, Immunological; Myeloid Cells; Phagocytes; Phagocytosis; Receptors, Immunologic; Signal Transduction; Toll-Like Receptors
PubMed: 22699831
DOI: 10.1038/nri3244 -
Viruses Jun 2017Phagocytes are the main component of innate immunity. They remove pathogens and particles from organisms using their bactericidal tools in the form of both reactive... (Review)
Review
Phagocytes are the main component of innate immunity. They remove pathogens and particles from organisms using their bactericidal tools in the form of both reactive oxygen species and degrading enzymes-contained in granules-that are potentially toxic proteins. Therefore, it is important to investigate the possible interactions between phages and immune cells and avoid any phage side effects on them. Recent progress in knowledge concerning the influence of phages on phagocytes is also important as such interactions may shape the immune response. In this review we have summarized the current knowledge on phage interactions with phagocytes described so far and their potential implications for phage therapy The data suggesting that phage do not downregulate important phagocyte functions are especially relevant for the concept of phage therapy.
Topics: Bacteriophages; Dendritic Cells; Humans; Immunity, Innate; Monocytes; Phage Therapy; Phagocytes; Phagocytosis
PubMed: 28613272
DOI: 10.3390/v9060150 -
Ageing Research Reviews Sep 2013Immunologically-silent phagocytosis of apoptotic cells is critical to maintaining tissue homeostasis and innate immune balance. Aged phagocytes reduce their functional... (Review)
Review
Immunologically-silent phagocytosis of apoptotic cells is critical to maintaining tissue homeostasis and innate immune balance. Aged phagocytes reduce their functional activity, leading to accumulation of unphagocytosed debris, chronic sterile inflammation and exacerbation of tissue aging and damage. Macrophage dysfunction plays an important role in immunosenescence. Microglial dysfunction has been linked to age-dependent neurodegenerations. Retinal pigment epithelial (RPE) cell dysfunction has been implicated in the pathogenesis of age-related macular degeneration (AMD). Despite several reports on the characterization of aged phagocytes, the role of phagocyte dysfunction in tissue aging and degeneration is yet to be fully appreciated. Lack of knowledge of molecular mechanisms by which aging reduces phagocyte function has hindered our capability to exploit the therapeutic potentials of phagocytosis for prevention or delay of tissue degeneration. This review summarizes our current knowledge of phagocyte dysfunction in aged tissues and discusses possible links to age-related diseases. We highlight the challenges to decipher the molecular mechanisms, present new research approaches and envisage future strategies to prevent phagocyte dysfunction, tissue aging and degeneration.
Topics: Aging; Animals; Apoptosis; Cellular Senescence; Humans; Macular Degeneration; Phagocytes; Phagocytosis; Retinal Pigment Epithelium
PubMed: 23748186
DOI: 10.1016/j.arr.2013.05.006 -
Immunological Reviews Mar 2023Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating... (Review)
Review
Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating mechanisms is phagocytosis, the process of particle engulfment into a vacuole-like structure called the phagosome. The antimicrobial activity of the phagocytic process results from a collaboration of multiple systems and mechanisms within this organelle, where a complex interplay of ion fluxes, pH, reactive oxygen species, and antimicrobial proteins creates a dynamic antimicrobial environment. This complexity, combined with the difficulties of studying neutrophils ex vivo, has led to gaps in our knowledge of how the neutrophil phagosome optimizes pathogen killing. In particular, controversy has arisen regarding the relative contribution and integration of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived antimicrobial agents and granule-delivered antimicrobial proteins. Clinical syndromes arising from dysfunction in these systems in humans allow useful insight into these mechanisms, but their redundancy and synergy add to the complexity. In this article, we review the current knowledge regarding the formation and function of the neutrophil phagosome, examine new insights into the phagosomal environment that have been permitted by technological advances in recent years, and discuss aspects of the phagocytic process that are still under debate.
Topics: Humans; Neutrophils; Phagosomes; Phagocytosis; Phagocytes; Reactive Oxygen Species
PubMed: 36440666
DOI: 10.1111/imr.13173 -
Frontiers in Endocrinology 2020Atherosclerosis (AS) is the main pathological basis for the development of cardio-cerebrovascular diseases. Abnormal accumulation of apoptotic and necrotic cells... (Review)
Review
Atherosclerosis (AS) is the main pathological basis for the development of cardio-cerebrovascular diseases. Abnormal accumulation of apoptotic and necrotic cells resulted in plaque enlargement, necrotic core formation and plaque rupture in AS. Under physiological conditions, apoptotic cells (ACs) could be effectively phagocytized and cleared by phagocyte-mediated efferocytosis. In contrast, the clearance efficiency of ACs in AS plaque was much lower because of the impaired efferocytosis in AS. Recent findings have made great progress on the molecular mechanisms of efferocytosis process and dynamic regulation, and its dysfunction on organismal health. Yet, there are still few effective treatments for this process. This article reviews the mechanism of efferocytosis and the role of efferocytosis in AS, highlighting a novel therapeutic strategy for AS, which mainly prevents the progression of plaque by targeting efferocytosis.
Topics: Animals; Apoptosis; Atherosclerosis; Humans; Necrosis; Phagocytes; Phagocytosis
PubMed: 33597922
DOI: 10.3389/fendo.2020.585285 -
Nature Reviews. Immunology Jun 2010When Ralph Steinman and Zanvil Cohn first described dendritic cells (DCs) in 1973 it took many years to convince the immunology community that these cells were truly... (Review)
Review
When Ralph Steinman and Zanvil Cohn first described dendritic cells (DCs) in 1973 it took many years to convince the immunology community that these cells were truly distinct from macrophages. Almost four decades later, the DC is regarded as the key initiator of adaptive immune responses; however, distinguishing DCs from macrophages still leads to confusion and debate in the field. Here, Nature Reviews Immunology asks five experts to discuss the issue of heterogeneity in the mononuclear phagocyte system and to give their opinion on the importance of defining these cells for future research.
Topics: Animals; Biomarkers; Cell Culture Techniques; Dendritic Cells; Humans; Myeloid Cells; Phagocytes
PubMed: 20467425
DOI: 10.1038/nri2784 -
DNA and Cell Biology Feb 2021Effective and efficient efferocytosis of dead cells and associated cellular debris are critical to tissue homeostasis and healing of injured tissues. This important task... (Review)
Review
Effective and efficient efferocytosis of dead cells and associated cellular debris are critical to tissue homeostasis and healing of injured tissues. This important task was previously thought to be restricted to professional phagocytes (PPs). However, accumulating evidence has revealed another type of phagocyte, the amateur phagocyte (AP), which can also participate in efferocytosis. APs are non-myeloid progenitor/nonimmune cells that include differentiated cells (e.g., epithelial cells, fibroblasts, and endothelial cells [ECs]) and stem cells (e.g., neuronal progenitor cells and mesenchymal cells) and can be found throughout the human body. Studies have shown that APs have two prominent roles: identifying and removing dead cells presumably before PPs reach the site of injury and assisting PPs in the removal of cell corpses and the resolution of inflamed tissue. With respect to the engulfment and degradation of dead cells, APs are slower and less efficient than PPs. However, APs are fundamental to preventing the spread of inflammation over a large area. In this review, we present the diversity and characteristics of healthy and non-neoplastic APs in mammals. We also propose a hypothetical mechanism of the efferocytosis of immunoglobulin G (IgG)-opsonized myelin debris by ECs (APs). Furthermore, the ingestion and clearance of dead cells can induce proinflammatory or anti-inflammatory cytokine production, endothelial activation, and cellular fate transition, which contribute to the progression of disease. An understanding of the role of APs is necessary to develop effective intervention strategies, including potential molecular targets for clinical diagnosis and drug development, for inflammation-related diseases.
Topics: Animals; Humans; Phagocytes
PubMed: 33439750
DOI: 10.1089/dna.2020.5647