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International Journal of Nanomedicine 2015Nanoparticles (NPs) present in the environment and in consumer products can cause immunotoxic effects. The immune system is very complex, and in vivo studies are the... (Review)
Review
Nanoparticles (NPs) present in the environment and in consumer products can cause immunotoxic effects. The immune system is very complex, and in vivo studies are the gold standard for evaluation. Due to the increased amount of NPs that are being developed, cellular screening assays to decrease the amount of NPs that have to be tested in vivo are highly needed. Effects on the unspecific immune system, such as effects on phagocytes, might be suitable for screening for immunotoxicity because these cells mediate unspecific and specific immune responses. They are present at epithelial barriers, in the blood, and in almost all organs. This review summarizes the effects of carbon, metal, and metal oxide NPs used in consumer and medical applications (gold, silver, titanium dioxide, silica dioxide, zinc oxide, and carbon nanotubes) and polystyrene NPs on the immune system. Effects in animal exposures through different routes are compared to the effects on isolated phagocytes. In addition, general problems in the testing of NPs, such as unknown exposure doses, as well as interference with assays are mentioned. NPs appear to induce a specific immunotoxic pattern consisting of the induction of inflammation in normal animals and aggravation of pathologies in disease models. The evaluation of particle action on several phagocyte functions in vitro may provide an indication on the potency of the particles to induce immunotoxicity in vivo. In combination with information on realistic exposure levels, in vitro studies on phagocytes may provide useful information on the health risks of NPs.
Topics: Animals; Metal Nanoparticles; Nanoparticles; Nanotubes, Carbon; Oxides; Phagocytes; Silicon Dioxide; Silver; Titanium; Toxicity Tests; Zinc Oxide
PubMed: 26060398
DOI: 10.2147/IJN.S83068 -
Clinical and Experimental Immunology May 1993The C3 receptor CR3 is expressed on phagocytic cells, minor subsets of B and T cells, and natural killer (NK) cells. It has important functions both as an adhesion... (Review)
Review
The C3 receptor CR3 is expressed on phagocytic cells, minor subsets of B and T cells, and natural killer (NK) cells. It has important functions both as an adhesion molecule and a membrane receptor mediating recognition of diverse ligands such as intercellular adhesion molecule-1 (ICAM-1) and fixed iC3b. The receptor is capable of undergoing an activation event that regulates both its specificity for various ligands and its ability to mediate phagocytosis or extracellular cytotoxicity. Certain bacteria express carbohydrates or lipopolysaccharides (LPS) that can bind to and activate CR3, allowing the receptor to assume its activated state. Soluble beta-glucan derived from the yeast Saccharomyces cerevisiae is a particularly potent stimulator of CR3, and produces an activated state of the receptor that permits neutrophil phagocytosis of iC3b-coated erythrocytes or NK, cell cytotoxicity of iC3b-coated tumour cells, that are normally resistant to NK cells.
Topics: Cell Degranulation; Humans; Integrins; Killer Cells, Natural; Ligands; Macrophage-1 Antigen; Phagocytes; Phagocytosis; Respiratory Burst
PubMed: 8485905
DOI: 10.1111/j.1365-2249.1993.tb03377.x -
Methods in Molecular Biology (Clifton,... 2020Phagocytosis by phagocytes such as neutrophils is a crucial part of the host innate immune response against invading pathogens. Phagocytosis is a complex process that...
Phagocytosis by phagocytes such as neutrophils is a crucial part of the host innate immune response against invading pathogens. Phagocytosis is a complex process that initiates with the binding of the particles on the cell surface of the phagocytes through the interaction of pattern recognition receptors with ligands on the surface of the pathogens. During this process, phagocytes undergo extensive membrane reorganization and cytoskeleton rearrangement at their cell surface. To gain better insight about the molecular mechanisms of this dynamic cellular process, visualization and quantification in a high-throughput manner is essential. Here, we describe a microscope-based method to visualize and quantify phagocytic uptake of pathogens (such as bacteria and fungi) and model particulates that are larger than 0.5 μm (such as Zymosan A and IgG-coated beads).
Topics: Biomarkers; Cell Differentiation; Cell Line; Cell Tracking; Fluorescent Antibody Technique; High-Throughput Screening Assays; Humans; Image Processing, Computer-Assisted; Neutrophils; Optical Imaging; Phagocytes; Phagocytosis
PubMed: 31728989
DOI: 10.1007/978-1-0716-0154-9_11 -
Clinical and Experimental Immunology Jul 1996Since Aschoff's reticuloendothelial system was abandoned a few decades ago, classification and characterization of the mononuclear phagocyte and dendritic cell systems... (Comparative Study)
Comparative Study Review
Since Aschoff's reticuloendothelial system was abandoned a few decades ago, classification and characterization of the mononuclear phagocyte and dendritic cell systems have evolved separately or even in competition with one another. New information has now become available indicating that monocytes/macrophages and dendritic cells have a common origin in the bone marrow, and may even transdifferentiate. Morphological and functional distinctions-although valid under certain conditions-have been blurred by revelation of the versatility of monocytes/macrophages and dendritic cells in response to different contextual needs in inflammation and immunity. Monocytes/macrophages and dendritic cells share a sentinel, receptor/effector, and presentation mode, and may either activate or silence specific immune reactions. In keeping with the view of monocytes/macrophages and dendritic cells as interactive sentinels, we suggest that the mono-nuclear phagocyte and dendritic cell systems be replaced by the custocyte system (custos, Lat = sentinel, guard) as a unifying concept. Within the custocyte system, we recognize type I, type II, and type III custocytes. Type I and II custocytes exhibit predominance of presentation or effector/presenter interdependency, respectively, while type III custocytes are bipolar, passing through type I- and type II-like phases during their development and in inflammatory responses. The custocyte system brings into view monocytes/macrophages and dendritic cells as dynamic players in immunity and inflammation with a high degree of derivational, phenotypic, functional, and molecular plasticity.
Topics: Animals; Cell Differentiation; Dendritic Cells; Humans; Phagocytes
PubMed: 8697614
DOI: 10.1046/j.1365-2249.1996.d01-740.x -
I'm Infected, Eat Me! Innate Immunity Mediated by Live, Infected Cells Signaling To Be Phagocytosed.Infection and Immunity Apr 2021Innate immunity against pathogens is known to be mediated by barriers to pathogen invasion, activation of complement, recruitment of immune cells, immune cell... (Review)
Review
Innate immunity against pathogens is known to be mediated by barriers to pathogen invasion, activation of complement, recruitment of immune cells, immune cell phagocytosis of pathogens, death of infected cells, and activation of the adaptive immunity via antigen presentation. Here, we propose and review evidence for a novel mode of innate immunity whereby live, infected host cells induce phagocytes to phagocytose the infected cell, thereby potentially reducing infection. We discuss evidence that host cells, infected by virus, bacteria, or other intracellular pathogens (i) release nucleotides and chemokines as find-me signals, (ii) expose on their surface phosphatidylserine and calreticulin as eat-me signals, (iii) release and bind opsonins to induce phagocytosis, and (iv) downregulate don't-eat-me signals CD47, major histocompatibility complex class I (MHC1), and sialic acid. As long as the pathogens of the host cell are destroyed within the phagocyte, then infection can be curtailed; if antigens from the pathogens are cross-presented by the phagocyte, then an adaptive response would also be induced. Phagocytosis of live infected cells may thereby mediate innate immunity.
Topics: Adaptive Immunity; Animals; Antigen Presentation; Biomarkers; Cross-Priming; Host-Pathogen Interactions; Humans; Immunity, Innate; Phagocytes; Phagocytosis; Signal Transduction
PubMed: 33558325
DOI: 10.1128/IAI.00476-20 -
Mediators of Inflammation 2016Professional mononuclear phagocytes such as polymorphonuclear neutrophils (PMN), monocytes, and macrophages are considered as the first line of defence against invasive... (Review)
Review
Professional mononuclear phagocytes such as polymorphonuclear neutrophils (PMN), monocytes, and macrophages are considered as the first line of defence against invasive pathogens. The formation of extracellular traps (ETs) by activated mononuclear phagocytes is meanwhile well accepted as an effector mechanism of the early host innate immune response acting against microbial infections. Recent investigations showed evidence that ETosis is a widely spread effector mechanism in vertebrates and invertebrates being utilized to entrap and kill bacteria, fungi, viruses, and protozoan parasites. ETs are released in response to intact protozoan parasites or to parasite-specific antigens in a controlled cell death process. Released ETs consist of nuclear DNA as backbone adorned with histones, antimicrobial peptides, and phagocyte-specific granular enzymes thereby producing a sticky extracellular matrix capable of entrapping and killing pathogens. This review summarizes recent data on protozoa-induced ETosis. Special attention will be given to molecular mechanisms of protozoa-induced ETosis and on its consequences for the parasites successful reproduction and life cycle accomplishment.
Topics: Animals; Humans; Phagocytes; Phagocytosis; Protozoan Infections
PubMed: 27445437
DOI: 10.1155/2016/5898074 -
Biochimica Et Biophysica Acta Aug 2006The phagocyte NADPH oxidase produces superoxide anion (O(2)(.-)) by the electrogenic process of moving electrons across the cell membrane. This charge translocation must... (Review)
Review
The phagocyte NADPH oxidase produces superoxide anion (O(2)(.-)) by the electrogenic process of moving electrons across the cell membrane. This charge translocation must be compensated to prevent self-inhibition by extreme membrane depolarization. Examination of the mechanisms of charge compensation reveals that these mechanisms perform several other vital functions beyond simply supporting oxidase activity. Voltage-gated proton channels compensate most of the charge translocated by the phagocyte NADPH oxidase in human neutrophils and eosinophils. Quantitative modeling of NADPH oxidase in the plasma membrane supports this conclusion and shows that if any other conductance is present, it must be miniscule. In addition to charge compensation, proton flux from the cytoplasm into the phagosome (a) helps prevent large pH excursions both in the cytoplasm and in the phagosome, (b) minimizes osmotic disturbances, and (c) provides essential substrate protons for the conversion of O(2)(*-) to H(2)O(2) and then to HOCl. A small contribution by K+ or Cl- fluxes may offset the acidity of granule contents to keep the phagosome pH near neutral, facilitating release of bactericidal enzymes. In summary, the mechanisms used by phagocytes for charge compensation during the respiratory burst would still be essential to phagocyte function, even if NADPH oxidase were not electrogenic.
Topics: Animals; Cell Membrane; Humans; Kinetics; NADPH Oxidases; Neutrophils; Phagocytes; Reactive Oxygen Species; Respiratory Burst; Superoxides
PubMed: 16483534
DOI: 10.1016/j.bbabio.2006.01.005 -
Journal of Clinical Pathology Jul 1983The granulomatous inflammatory response is a special type of chronic inflammation characterised by often focal collections of macrophages, epithelioid cells and... (Review)
Review
The granulomatous inflammatory response is a special type of chronic inflammation characterised by often focal collections of macrophages, epithelioid cells and multinucleated giant cells. In this review the characteristics of these cells of the mononuclear phagocyte series are considered, with particular reference to the properties of epithelioid cells and the formation of multinucleated giant cells. The initiation and development of granulomatous inflammation is discussed, stressing the importance of persistence of the inciting agent and the complex role of the immune system, not only in the perpetuation of the granulomatous response but also in the development of necrosis and fibrosis.
Topics: Granuloma; Granuloma, Giant Cell; Humans; Macrophage Activation; Macrophages; Monocytes; Necrosis; Phagocytes; Phagocytosis; Pinocytosis
PubMed: 6345591
DOI: 10.1136/jcp.36.7.723 -
Seminars in Immunopathology Nov 2018An internal system designed to ward off and remove unnecessary or hazardous materials is intrinsic to animals. In addition to exogenous pathogens, a number of... (Review)
Review
An internal system designed to ward off and remove unnecessary or hazardous materials is intrinsic to animals. In addition to exogenous pathogens, a number of self-molecules, such as apoptotic or necrotic dead cells, their debris, and the oxides or peroxides of their cellular components, are recognized as extraneous substances. It is essential to eliminate these internal pathogens as quickly as possible because their accumulation can cause chronic inflammation as well as autoimmune responses, possibly leading to onset or progression of certain diseases. Apoptosis inhibitor of macrophage (AIM, also called CD5L) is a circulating protein that is a member of the scavenger receptor cysteine-rich superfamily, and we recently found that during acute kidney injury, AIM associates with intraluminal dead cell debris accumulated in renal proximal tubules and enhances clearance of luminal obstructions, thereby facilitating repair. Thus, AIM acts as a marker for phagocytes so that they can efficiently recognize and engulf the debris as their targets. In this chapter, we give an overview of the professional and non-professional phagocytes, and how soluble scavenging molecules such as AIM contribute to improvement of diseases by stimulating phagocytic activity.
Topics: Acute Kidney Injury; Animals; Apoptosis Regulatory Proteins; Biomarkers; Disease Susceptibility; Humans; Inhibitor of Apoptosis Proteins; Ligands; Macrophages; Phagocytes; Phagocytosis; Receptors, Scavenger; Scavenger Receptors, Class B
PubMed: 30310974
DOI: 10.1007/s00281-018-0717-6 -
Immunological Reviews May 2020We have only recently started to appreciate the extent to which immune cell activation involves significant changes in cellular metabolism. We are now beginning to... (Review)
Review
We have only recently started to appreciate the extent to which immune cell activation involves significant changes in cellular metabolism. We are now beginning to understand how commitment to specific metabolic pathways influences aspects of cellular biology that are the more usual focus of immunological studies, such as activation-induced changes in gene transcription, post-transcriptional regulation of transcription, post-translational modifications of proteins, cytokine secretion, etc. Here, we focus on metabolic reprogramming in mononuclear phagocytes downstream of stimulation with inflammatory signals (such as LPS and IFNγ) vs alternative activation signals (IL-4), with an emphasis on work on dendritic cells and macrophages from our laboratory, and related studies from others. We cover aspects of glycolysis and its branching pathways (glycogen synthesis, pentose phosphate, serine synthesis, hexose synthesis, and glycerol 3 phosphate shuttle), the tricarboxylic acid pathway, fatty acid synthesis and oxidation, and mitochondrial biology. Although our understanding of the metabolism of mononuclear phagocytes has progressed significantly over the last 10 years, major challenges remain, including understanding the effects of tissue residence on metabolic programming related to cellular activation, and the translatability of findings from mouse to human biology.
Topics: Animals; Energy Metabolism; Humans; Macrophage Activation; Macrophages; Mononuclear Phagocyte System; Phagocytes
PubMed: 32242952
DOI: 10.1111/imr.12848