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Journal of Leukocyte Biology Jan 2010The antimicrobial effector activity of phagocytes is crucial in the host innate defense against infection, and the classic view is that the phagocytes operating against... (Review)
Review
The antimicrobial effector activity of phagocytes is crucial in the host innate defense against infection, and the classic view is that the phagocytes operating against intracellular and extracellular microbial pathogens are,respectively, macrophages and neutrophils. As a result of the common origin of the two phagocytes, they share several functionalities, including avid phagocytosis,similar kinetic behavior under inflammatory/infectious conditions, and antimicrobial and immunomodulatory activities. However, consequent to specialization during their differentiation, macrophages and neutrophils acquire distinctive, complementary features that originate different levels of antimicrobial capacities and cytotoxicity and different tissue localization and lifespan.This review highlights data suggesting the perspective that the combination of overlapping and complementary characteristics of the two professional phagocytes promotes their cooperative participation as effectors and modulators in innate immunity against infection and as orchestrators of adaptive immunity. In the concerted activities operating in antimicrobial innate immunity, macrophages and neutrophils are not able to replace each other. The common and complementary developmental,kinetic, and functional properties of neutrophils and macrophages make them the effector arms of a myeloid phagocyte system that groups neutrophils with members of the old mononuclear phagocyte system. The use by mammals of a system with two dedicated phagocytic cells working cooperatively represents an advantageous innate immune attack strategy that allows the efficient and safe use of powerful but dangerous microbicidal molecules.This crucial strategy is a target of key virulence mechanisms of successful pathogens.
Topics: Animals; Bacterial Infections; Cell Communication; Cell Lineage; Cell Movement; Humans; Immunity, Innate; Inflammation; Macrophages; Mammals; Myeloid Cells; Neutrophils; Parasitic Diseases; Phagocytosis
PubMed: 20052802
DOI: 10.1189/jlb.0809549 -
Annals of the New York Academy of... Dec 1997
Review
Topics: Animals; Brain Neoplasms; Glioma; Humans; Macrophages; Microglia; Monocytes; Phagocytes
PubMed: 9704068
DOI: 10.1111/j.1749-6632.1997.tb46268.x -
Journal of Molecular Medicine (Berlin,... Aug 2009The formation of extracellular traps (ETs) by phagocytic cells has been recognized as a novel and important mechanism of the host innate immune response against... (Review)
Review
The formation of extracellular traps (ETs) by phagocytic cells has been recognized as a novel and important mechanism of the host innate immune response against infections. ETs are formed by different host immune cells such as neutrophils, mast cells, and eosinophils after stimulation with mitogens, cytokines, or pathogens themselves, in a process dependent upon induction of a reactive-oxygen-species-mediated signaling cascade. ETs consist of nuclear or mitochondrial DNA as a backbone with embedded antimicrobial peptides, histones, and cell-specific proteases and thereby provide a matrix to entrap and kill microbes and to induce the contact system. This review summarizes the latest research on ETs and their role in innate immunity and host innate defense. Attention is also given to mechanisms by which certain leading bacterial pathogens have evolved to avoid entrapment and killing in these specialized structures.
Topics: Animals; Bacterial Physiological Phenomena; Extracellular Space; Host-Pathogen Interactions; Humans; Immunity, Innate; Phagocytes
PubMed: 19444424
DOI: 10.1007/s00109-009-0481-0 -
Seminars in Diagnostic Pathology Feb 1990The phagocytic activity of macrophages and related cells has been recognized for over a century. Within the last decade a variety of other functions has been attributed... (Review)
Review
The phagocytic activity of macrophages and related cells has been recognized for over a century. Within the last decade a variety of other functions has been attributed to these same cell types. Examples include antigen processing and antigen presentation to B and T cells, and synthesis of a large number of immunoregulatory proteins. This recent explosion of information regarding the functions and cell types of this complex cell system has had little impact on the practice of pathology in that nomenclature, concepts of disease classification, and our diagnostic approach to the majority of "histiocytic" disorders have not been revised. As the mysteries of this complex cell system are unraveled, older names, such as the mononuclear phagocyte system that focus on only one function, have become obsolete. Because recent evidence shows that this cell system also plays a pivotal and multifaceted role in immunity, the designation mononuclear phagocyte and immunoregulatory effector (M-PIRE) system is recommended. Diverse cell types, including bone marrow precursor cells, histiocytes, various dendritic cells, and Langerhans cells, comprise the M-PIRE system, and these are located in tissues throughout the body. Although mature macrophages and dendritic cells are strikingly different in morphology and function, evidence from studies of both normal cells and proliferative disorders suggests a common cell of origin. There also is provocative evidence suggesting that transitions between cell types may occur, analogous to those observed in the lymphoid cell system. In this report, a conceptual overview of the M-PIRE system including origin, normal function, proposed transitional cell forms, and disease states is presented.
Topics: Animals; Cell Division; Diagnosis, Differential; Humans; Immune System; Immune System Diseases; Lymphoma; Neoplasms; Pathology; Phagocytes
PubMed: 2180013
DOI: No ID Found -
Journal of Neuroimmunology Mar 1998The literature describing effects of morphine on cells of the immune system points to the clear conclusion that morphine given in vivo suppresses a variety of immune... (Review)
Review
The literature describing effects of morphine on cells of the immune system points to the clear conclusion that morphine given in vivo suppresses a variety of immune responses that involve the major cell types in the immune system, including natural killer (NK) cells, T cells, B cells, macrophages and polymorphonuclear leukocytes (PMNs). Depression of NK cell activity has been reported in humans, monkeys and rodents. Similarly, responses of T cells are depressed by morphine, as assessed by inhibition of induction of delayed-type hypersensitivity reactions and cytotoxic T-cell activity, modulation of T-cell antigen expression, and depression of responses to T-cell mitogens. Effects on T cells have been reported in humans, monkeys and rodents. Effects of morphine on B-cell activity have mainly been tested in rodents using assays of antibody formation, which also require macrophages and T cells, preventing a conclusion as to the cell type being affected. Consistent effects on phagocytic cell function have been reported in rodents given morphine. In contrast, studies on immunomodulatory effects of morphine added to cells of the immune system in vitro have shown robust effects on some of these cell types, but not others. There is a rich literature demonstrating downregulation of phagocytic cell function by morphine, particularly for human peripheral blood mononuclear cells (PBMCs) and PMNs. Phagocytosis, chemotactic responses, interleukin production, and generation of activated oxygen intermediates and arachidonic acid products have all been reported to be inhibited. On the contrary, the literature does not support direct effects of morphine on NK cell function, is inconclusive concerning effects on B cells, and provides limited evidence for effects on T cells. The divergence between the in vivo and in vitro data suggests that effects on some cells in the immune system observed after in vivo morphine are probably not direct, but mediated. In aggregate, the literature supports the existence of an in vivo neural-immune circuit through which morphine acts to depress the function of all cells of the immune system. Further, there is strong evidence that morphine can directly depress the function of macrophages and PMNs, and modulate expression of one type of T-cell surface marker. There is, however, little evidence for direct effects of morphine on NK cells and B cells. A further complication emerges from reports of immunopotentiation of immune function in in vitro assays using endogenous opioids. The possibility of different receptors for endogenous and exogenous opioids or of interactions among the activated opioid receptors may account for these opposing effects.
Topics: Humans; Lymphocytes; Macrophages; Morphine; Narcotics; Neuroimmunomodulation; Phagocytes
PubMed: 9610671
DOI: 10.1016/s0165-5728(97)00219-1 -
Archives of Dermatology Nov 1976An increasing number of phagocytic defects with cutaneous manifestations and signs in humans are being reported. With the increasing availability of phagocyte assays,...
An increasing number of phagocytic defects with cutaneous manifestations and signs in humans are being reported. With the increasing availability of phagocyte assays, detection of phagocyte defects will allow us to dissect the component events and more clearly understand the central role of the phagocytic leukocyte in host defenses of the skin.
Topics: Acrodermatitis; Cell Movement; Chediak-Higashi Syndrome; Chemotaxis; Humans; Hypergammaglobulinemia; Immunity, Cellular; Immunoglobulin E; Inflammation; Melanoma; Phagocyte Bactericidal Dysfunction; Phagocytes; Phagocytosis; Wiskott-Aldrich Syndrome
PubMed: 984866
DOI: No ID Found -
Blood Reviews Jun 1989Advances in molecular genetic understanding of disease processes has been extended to a number of phagocytic disorders. Most of these disorders were extensively... (Review)
Review
Advances in molecular genetic understanding of disease processes has been extended to a number of phagocytic disorders. Most of these disorders were extensively characterized at the functional and protein level prior to cloning of the relevant genes. Nucleotide sequence data has been essential for establishing the mechanism and mode of inheritance of genetically transmitted phagocyte disorders. Such data provides insights into the functionally important regions of affected proteins and information regarding regulation of these genes and homologies to other known proteins. From such data it is also possible to determine the evolutionary history of these genes. Chronic granulomatous disease, a phenotypic classification of a heterogeneous group of defects in oxidative metabolism, has now been defined in terms of specific molecular defects. Cloning of the two subunits of cytochrome b558 has led the way to characterization of the X-linked form and one of the autosomal recessive forms of this disease and confirmed the importance of this protein in the phagocyte oxidative burst. The absence of lactoferrin associated with hereditary specific granule deficiency is a result of decreased transcription of the lactoferrin gene in myeloid cells. Myeloperoxidase deficiency is likely a result of a mutation of the gene coding for myeloperoxidase. More precise understanding of expression of the lactoferrin and myeloperoxidase genes may be important in elucidating some of the underlying mechanisms in the pathogenesis of myeloid malignancies. A rare disorder, leukocyte adhesion deficiency, has provided a model for establishing the relationship between the several distinct alpha subunits and the shared common beta subunit of leukocyte adhesion proteins. These proteins have been shown to be genetically related to the superfamily of extracellular matrix receptors termed 'integrins'. Because these proteins have been highly conserved at the genetic level across a variety of species, comparison of nucleotide sequence data has illuminated some of the evolutionary history of these genes as they arose from ancestral genes. Studies of these adhesion protein genes may contribute new information in the broader context of how the functions of these genes evolved.
Topics: Humans; Immune System Diseases; Phagocytes
PubMed: 2673450
DOI: 10.1016/0268-960x(89)90004-0 -
Science (New York, N.Y.) Sep 1982For unknown reasons, humans infected with the bacterium Bordetella pertussis are exceptionally vulnerable to secondary infections. Bordetella species elaborate a...
For unknown reasons, humans infected with the bacterium Bordetella pertussis are exceptionally vulnerable to secondary infections. Bordetella species elaborate a soluble, heat-stable, and highly active adenylate cyclase. This enzyme is internalized by phagocytic cells and catalyzes the unregulated formation of adenosine 3',5'-monophosphate (cyclic AMP), thereby disrupting normal cellular function. This unusual phenomenon may explain Bordetella-induced aphylaxis and may prove to be useful for investigating a variety of cyclic AMP-governed processes.
Topics: Adenylyl Cyclases; Animals; Bordetella pertussis; Cells, Cultured; Cyclic AMP; Humans; Macrophages; Neutrophils; Phagocytes; Rabbits; Superoxides; Temperature
PubMed: 6287574
DOI: 10.1126/science.6287574 -
Reviews of Infectious Diseases 1980
Topics: Bacteria; Chemotaxis, Leukocyte; Eosinophils; Humans; Lysosomes; Macrophages; Monocytes; Neutrophils; Phagocytes; Phagocytosis
PubMed: 7052569
DOI: 10.1093/clinids/2.5.817 -
Experientia Oct 1988Simple testing models have been developed for the evaluation of chemical or biological compounds that modulate the activity of human phagocytes. Human neutrophils from... (Review)
Review
Simple testing models have been developed for the evaluation of chemical or biological compounds that modulate the activity of human phagocytes. Human neutrophils from buffy coats of donor blood are used. They are stimulated with receptor agonists, and the effects of test compounds on exocytosis of different enzymes, the generation of superoxide (respiratory burst), and cytotoxicity are quantified. All assays are performed in microtiter plates and the responses are evaluated by multi-well photometry or fluorimetry. The models are apt to detect compounds acting on phagocytes as agonists or antagonists, signal transduction activators or inhibitors and primers of agonist responses, and to assess cytotoxic effects.
Topics: Cell Survival; Exocytosis; Humans; Hydrogen Peroxide; Neutrophils; Pancreatic Elastase; Phagocytes
PubMed: 3053230
DOI: 10.1007/BF01941181