Chapter 9: Microspheres and Phagocytosis
Zoltán A. Tökés in Micro spheres: Medical and Biological Applications, 2017
This chapter reviews the phagocytic process and discusses the advantages, applications, and limitations of the utilization of microspheres in the study of phagocytosis. The most active mononuclear phagocytes are the promocytes in the bone marrow which enter the blood as monocytes. Light and transmission electron microscopy, utilization of large microspheres, and treatment of fixed phagocyte cells with xylene, chloroform, or dioxane to dissolve extracellular polystyrene particles are among the techniques that have been utilized for this purpose. The phagocytic process can be divided into three general phases: the attachment of foreign particles to the surface of the phagocytic cell, the ingestion of such particles by the phagocytes, and the digestion of the ingested material within the cell. One of the major energetic factors to consider about phagocytosis with respect to small particles is their translational kinetic energy. Electronic analysis and recording of measurements may be performed with or without cell sorting.
Basic Knowledge of Host Defenses Against Infection
M. T. Labro in Host Defense and Infection, 2022
Multicellular organisms find themselves surrounded by single-cell microbes, only some of which are pathogenic. Phylogenic evolution has selected several features that protect the host from aggressive intruders. Human beings and mammals, at the top of the phylogenetic tree, possess these three levels of defense, and they are potent enough to protect them from most pathogens. “Innate immunity” refers to natural resistance to infection regardless of the pathogen and is immediately triggered when the protective barriers are breached. In the late 19th century, Metchnikoff recognized phagocytosis as a crucial mechanism in antibacterial defense. The term “professional phagocytes” covers cells whose main functions are engulfing and destroying foreign materials. Mast cells derived from multipotent stem cells play an important role in the inflammatory reaction by secreting a variety of mediators.
CASE 10 X-linked Agammaglobulinemia
Raif Geha, FRED Rosen in Case Studies in Immunology, 2008
Fig. 10.6 Encapsulated bacteria are efficiently engulfed by phagocytes only when they are coated with complement. Encapsulated bacteria resist ingestion by phagocytes unless they are recognized by antibodies that fix complement. IgG2 antibodies are produced against these bacteria in humans, and lead to the deposition of complement component C3b on the bacterial surface, where it is cleaved by Factor H and Factor I to produce iC3b, still bound to the bacterial surface. iC3b binds a specific receptor on phagocytes and induces the engulfment and destruction of the iC3b bacterium. Phagocytes also have receptors for C3b, but these are most effective when acting in concert with Fc receptors for IgG1 antibodies, whereas the iC3b receptor is potent enough to act alone, and is the most important receptor for the phagocytosis of pyogenic bacteria.
Regulation of phagocytosis by Rho GTPases
Published in Small GTPases, 2015
Yingyu Mao, Silvia C Finnemann
Phagocytosis is defined as a cellular uptake pathway for particles of greater than 0.5 μm in diameter. Particle clearance by phagocytosis is of critical importance for tissue health and homeostasis. The ultimate goal of anti-pathogen phagocytosis is to destroy engulfed bacteria or fungi and to stimulate cell-cell signaling that mount an efficient immune defense. In contrast, clearance phagocytosis of apoptotic cells and cell debris is anti-inflammatory. High capacity clearance phagocytosis pathways are available to professional phagocytes of the immune system and the retina. Additionally, a low capacity, so-called bystander phagocytic pathway is available to most other cell types. Different phagocytic pathways are stimulated by particle ligation of distinct surface receptors but all forms of phagocytosis require F-actin recruitment beneath tethered particles and F-actin re-arrangement promoting engulfment, which are controlled by Rho family GTPases. The specificity of Rho GTPase activity during the different forms of phagocytosis by mammalian cells is the subject of this review.
The Effect of Temperature, Metabolic Inhibitors, and EDTA on Phagocytosis of Polystyrene Latex Particles by Human Leucocytes
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 1969
A modified method of Roberts & Quastel has been used to study the influence of temperature, metabolic inhibitors and EDTA on human leucocyte phagocytosis. The phagocytosis was increased by raising the temperature from 4° to 37° C. 2-deoxy-D-glucose inhibited phagocytosis. Antimycin or oligomycin had no influence. The greatest inhibition of phagocytosis was obtained by a combination of 2-deoxy-D-glucose and antimycin or oligomycin, demonstrating that the energy may derive from both glycolysis and respiration, the main source being glycolytic energy. Increasing concentrations of EDTA from 2 to 4 mM as final concentrations decreased phagocytosis.
SPECIFIC NON-COPLANAR PCB-MEDIATED MODULATION OF BOTTLENOSE DOLPHIN AND BELUGA WHALE PHAGOCYTOSIS UPON IN VITRO EXPOSURE
Published in Journal of Toxicology and Environmental Health, Part A, 2004
Milton Levin, Brenda Morsey, Chiharu Mori, Sylvain Guise
Contaminant-induced immunosuppression by organochlorines (OC), particularly polychlorinated biphenyls (PCBs), has been suspected as a cofactor in the deaths of thousands of marine mammals. One important innate defense mechanism is phagocytosis, the ability of cells to ingest extracellular macromolecules. The present study was aimed at characterizing the immunomodulatory potential of representative OCs on phagocytosis in bottlenose dolphins and beluga whales. The ability of peripheral blood leukocytes to engulf fluorescent microspheres was evaluated using flow cytometry. The immunomodulatory effects of three non-coplanar PCB congeners, 138, 153, and 180, one coplanar PCB, 169, and 2,3,7,8-TCDD and all possible mixtures (26) were tested upon in vitro exposure. In both species, all mixtures containing at least two non-coplanar PCBs significantly reduced both neutrophil and monocyte phagocytosis, with effects more marked in dolphins than in belugas. Coplanar OCs, on their own or when added to non-coplanar congeners, did not further modulate phagocytosis, suggesting an Ah receptor-independent mechanism. Concentration-response experiments with individual congeners further demonstrated a non-coplanar PCB-induced suppression of phagocytosis, while coplanar congeners produced no consistent effects. Our results suggest simple additive interactions of chemicals in a mixture. However, calculation of toxic equivalency (TEQs) failed to predict the experimentally induced immunomodulatory effects of OCs on dolphin and beluga phagocytosis, confirming the Ah receptor-independent nature of the effects on phagocytosis. Overall, our results suggest that non-AhR mechanisms may explain one facet of immunotoxicity (phagocytosis), something that is not captured using the TEQ approach. This is the first report demonstrating the immunomodulatory effects of OCs on dolphin and beluga phagocytosis, and the first overall demonstration of immunomodulatory effects on phagocytosis mediated specifically by non-coplanar PCBs.