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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 -
Reviews of Infectious Diseases 1989Phagocytes play a key role in host defense, and cell defects are associated with increased susceptibility to infection. Flow cytometry offers rapid and reproducible... (Review)
Review
Phagocytes play a key role in host defense, and cell defects are associated with increased susceptibility to infection. Flow cytometry offers rapid and reproducible measurements of single cells in suspension and, following staining with one or more fluorochromes, simultaneous examination of several cell functions. Subpopulations of cells can be identified and sorted for morphologic, biochemical, and functional examination, and specially adapted computer systems allow storage of data for subsequent detailed analysis. Several flow-cytometric assays for the study of phagocytes and their interactions with microorganisms have been developed. These assays facilitate the study of (1) phagocyte surface receptors and regulatory molecules; (2) membrane potential; (3) phagocytosis of microorganisms, including the discrimination between attachment to the phagocyte surface and actual internalization; (4) phagosomal pH; (5) degranulation and enzymatic activity; (6) intracellular calcium; (7) oxidative metabolism; (8) intracellular killing of microorganisms; (9) degradation of microorganisms; and (10) exocytosis. In addition, the influence of serum opsonins on phagocyte-microorganism interactions can be studied. Flow-cytometric techniques are applicable to both experimental and clinical work.
Topics: Cell Separation; Flow Cytometry; Humans; Phagocytes
PubMed: 2644688
DOI: 10.1093/clinids/11.1.16 -
Journal of Periodontology Oct 1996A review of phagocytic cells-polymorphonuclear leukocytes and monocytes-in the inflammatory process is presented. Examples of phagocyte defect-related pathology serve as... (Review)
Review
A review of phagocytic cells-polymorphonuclear leukocytes and monocytes-in the inflammatory process is presented. Examples of phagocyte defect-related pathology serve as a framework for understanding the role of these cells in periodontal infection. The role of alterations in neutrophil function in localized juvenile periodontitis is presented as a model system for understanding periodontal pathology as a result of host-related functional abnormalities. Two topical alternative hypotheses for periodontal breakdown are presented in which macrophage control of the chronic lesion is altered by an absence of T cells or the influence of bacterial superantigens.
Topics: Aggressive Periodontitis; Antigens, Bacterial; Bacterial Infections; Humans; Macrophages; Monocytes; Neutrophils; Periodontal Diseases; Phagocytes; Superantigens; T-Lymphocytes
PubMed: 8910825
DOI: 10.1902/jop.1996.67.10s.1070 -
FEMS Microbiology Immunology Dec 1990
Topics: Animals; Bacterial Physiological Phenomena; Humans; Phagocytes; Phagocytosis
PubMed: 2073406
DOI: 10.1111/j.1574-6968.1990.tb03525.x -
American Journal of Respiratory Cell... Jul 2017The current paradigm in macrophage biology is that some tissues mainly contain macrophages from embryonic origin, such as microglia in the brain, whereas other tissues...
The current paradigm in macrophage biology is that some tissues mainly contain macrophages from embryonic origin, such as microglia in the brain, whereas other tissues contain postnatal-derived macrophages, such as the gut. However, in the lung and in other organs, such as the skin, there are both embryonic and postnatal-derived macrophages. In this study, we demonstrate in the steady-state lung that the mononuclear phagocyte system is comprised of three newly identified interstitial macrophages (IMs), alveolar macrophages, dendritic cells, and few extravascular monocytes. We focused on similarities and differences between the three IM subtypes, specifically, their phenotype, location, transcriptional signature, phagocytic capacity, turnover, and lack of survival dependency on fractalkine receptor, CXCR1. Pulmonary IMs were located in the bronchial interstitium but not the alveolar interstitium. At the transcriptional level, all three IMs displayed a macrophage signature and phenotype. All IMs expressed MER proto-oncogene, tyrosine kinase, CD64, CD11b, and CXCR1, and were further distinguished by differences in cell surface protein expression of CD206, Lyve-1, CD11c, CCR2, and MHC class II, along with the absence of Ly6C, Ly6G, and Siglec F. Most intriguingly, in addition to the lung, similar phenotypic populations of IMs were observed in other nonlymphoid organs, perhaps highlighting conserved functions throughout the body. These findings promote future research to track four distinct pulmonary macrophages and decipher the division of labor that exists between them.
Topics: Animals; Bone Marrow Cells; Dendritic Cells; Gene Expression Profiling; Lung; Macrophages; Macrophages, Alveolar; Mice, Inbred C57BL; Organ Specificity; Phagocytes; Phenotype; Transcription, Genetic
PubMed: 28257233
DOI: 10.1165/rcmb.2016-0361OC -
Developmental Cell Jul 2016Many phagocyte behaviors, including vascular rolling and adhesion, migration, and oxidative bursting, are better measured in seconds or minutes than hours or days....
Many phagocyte behaviors, including vascular rolling and adhesion, migration, and oxidative bursting, are better measured in seconds or minutes than hours or days. Zebrafish is ideally suited for imaging such rapid biology within the intact animal. We discuss how this model has revealed unique insights into various aspects of phagocyte physiology.
Topics: Animals; Disease Models, Animal; Humans; Neurons; Phagocytes; Zebrafish
PubMed: 27459065
DOI: 10.1016/j.devcel.2016.07.003 -
Mucosal Immunology Mar 2013At mucosal surfaces, phagocytes such as macrophages coexist with microbial communities; highly controlled regulation of these interactions is essential for immune... (Review)
Review
At mucosal surfaces, phagocytes such as macrophages coexist with microbial communities; highly controlled regulation of these interactions is essential for immune homeostasis. Pattern-recognition receptors (PRRs) are critical in recognizing and responding to microbial products, and they are subject to negative regulation through various mechanisms, including downregulation of PRR-activating components or induction of inhibitors. Insights into these regulatory mechanisms have been gained through human genetic disease-association studies, in vivo mouse studies utilizing disease models or targeted gene perturbations, and in vitro and ex vivo human cellular studies examining phagocytic cell functions. Although mouse models provide an important approach to study macrophage regulation, human and mouse macrophages exhibit differences, which must be considered when extrapolating mouse findings to human physiology. This review discusses inhibitory regulation of PRR-induced macrophage functions and the consequences of dysregulation of these functions and highlights mechanisms that have a role in intestinal macrophages and in human macrophage studies.
Topics: Animals; Cell Differentiation; Cell Movement; Homeostasis; Humans; Intestinal Mucosa; Intestines; Macrophages; Mice; Monocytes; Organ Specificity; Phagocytes; Receptors, Pattern Recognition; Signal Transduction
PubMed: 23340822
DOI: 10.1038/mi.2012.139 -
Apoptosis : An International Journal on... Sep 2010Recent evidence in humans indicate that defective phagocytic clearance of dying cells is linked to progression of advanced atherosclerotic lesions, the precursor to... (Review)
Review
Recent evidence in humans indicate that defective phagocytic clearance of dying cells is linked to progression of advanced atherosclerotic lesions, the precursor to atherothrombosis, ischemic heart disease, and leading cause of death in the industrialized world. During atherogenesis, apoptotic cell turnover in the vascular wall is counterbalanced by neighboring phagocytes with high clearance efficiency, thereby limiting cellularity and maintaining lesion integrity. However, as lesions mature, phagocytic removal of apoptotic cells (efferocytosis) becomes defective, leading to secondary necrosis, expansion of plaque necrotic cores, and susceptibility to rupture. Recent genetic causation studies in experimental rodents have implicated key molecular regulators of efferocytosis in atherosclerotic progression. These include MER tyrosine kinase (MERTK), milk fat globule-EGF factor 8 (MFGE8), and complement C1q. At the cellular level, atheromata are infiltrated by a heterogenous population of professional phagocytes, comprised of monocytes, differentiated macrophages, and CD11c(+) dendritic-like cells. Each cell type is characterized by disparate clearance efficiencies and varying activities of key phagocytic signaling molecules. It is in this context that we outline a working model whereby plaque necrosis and destabilization is jointly promoted by (1) direct inhibition of core phagocytic signaling pathways and (2) expansion of phagocyte subsets with poor clearance capacity. Towards identifying targets for promoting efficient apoptotic cell clearance and resolving inflammation in atherosclerosis and during ischemic heart disease and post myocardial infarction, this review will discuss potential in vivo suppressors of efferocytosis at each stage of clearance and how these putative interventional targets may differentially affect uptake at the level of vascular phagocyte subsets.
Topics: Animals; Apoptosis; Cardiovascular Diseases; Humans; Phagocytes; Phagocytosis
PubMed: 20552278
DOI: 10.1007/s10495-010-0516-6 -
Clinical Microbiology Reviews Oct 2000Professional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host... (Review)
Review
Professional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host defenses and various pathological settings characterized by excessive inflammation. Accordingly, they are key targets for immunomodulatory drugs, among which antibacterial agents are promising candidates. The basic and historical concepts of immunomodulation will first be briefly reviewed. Phagocyte complexity will then be unravelled (at least in terms of what we know about the origin, subsets, ambivalent roles, functional capacities, and transductional pathways of this cell and how to explore them). The core subject of this review will be the many possible interactions between antibacterial agents and phagocytes, classified according to demonstrated or potential clinical relevance (e.g., neutropenia, intracellular accumulation, and modulation of bacterial virulence). A detailed review of direct in vitro effects will be provided for the various antibacterial drug families, followed by a discussion of the clinical relevance of these effects in two particular settings: immune deficiency and inflammatory diseases. The prophylactic and therapeutic use of immunomodulatory antibiotics will be considered before conclusions are drawn about the emerging (optimistic) vision of future therapeutic prospects to deal with largely unknown new diseases and new pathogens by using new agents, new techniques, and a better understanding of the phagocyte in particular and the immune system in general.
Topics: Adjuvants, Immunologic; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Humans; Immunologic Factors; Phagocytes
PubMed: 11023961
DOI: 10.1128/CMR.13.4.615 -
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