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Clinical and Experimental Rheumatology 2021The aim of this study was to investigate the relationship between the degree of crystal phagocytosis and the magnitude of the local inflammatory process using fresh...
OBJECTIVES
The aim of this study was to investigate the relationship between the degree of crystal phagocytosis and the magnitude of the local inflammatory process using fresh synovial fluid (SF) collected from patients with crystal-induced arthritis. In parallel, an in vitro model of crystal-induced inflammation was used to assess the effect of cell priming on crystal phagocytosis and IL-1ß production.
METHODS
SF was collected from 20 patients with gout and 20 with pyrophosphate crystal-induced arthritis and examined under ordinary and polarised light microscopy for total and differential white blood cell (WBC) count and crystal search. The total phagocytosis index was determined in SF along with IL-1β, IL-8, IL-10, and TGFβ levels. The in vitro studies were performed using primed or unprimed THP-1 cells stimulated with calcium pyrophosphate (CPP) crystals, monosodium urate (MSU) crystals and/or cytochalasin D.
RESULTS
We demonstrated that the phagocytosis index calculated on the total number of cells was independent from the inflammatory local indices such as WBC and the percentage of polymorphonuclear cells but showed a positive correlation with pro-inflammatory cytokines. By contrast, the local inflammatory indices (WBC and IL-1ß) showed a strong positive correlation with the percentage of polymorphonuclear cells with crystals internalised and a negative correlation with the percentage of mononuclear cells with crystals internalised. The in vitro study showed that phagocytosis represents a fundamental step in the induction of the inflammatory response to MSU and CPP crystals, but it also occurs in absence of cell priming.
CONCLUSIONS
The results of this study indicate a possible role of non-inflammatory phagocytosis in limiting the acute attack of crystal-induced arthritis.
Topics: Gout; Humans; Inflammation; Phagocytosis; Synovial Fluid; Uric Acid
PubMed: 32828141
DOI: 10.55563/clinexprheumatol/jcmrd0 -
Proceedings of the National Academy of... Jun 2023Phagocytic clearance of degenerating neurons is triggered by "eat-me" signals exposed on the neuronal surface. The conserved neuronal eat-me signal phosphatidylserine...
Phagocytic clearance of degenerating neurons is triggered by "eat-me" signals exposed on the neuronal surface. The conserved neuronal eat-me signal phosphatidylserine (PS) and the engulfment receptor Draper (Drpr) mediate phagocytosis of degenerating neurons in . However, how PS is recognized by Drpr-expressing phagocytes in vivo remains poorly understood. Using multiple models of dendrite degeneration, we show that the chemokine-like protein Orion can bind to PS and is responsible for detecting PS exposure on neurons; it is supplied cell-non-autonomously to coat PS-exposing dendrites and to mediate interactions between PS and Drpr, thus enabling phagocytosis. As a result, the accumulation of Orion on neurons and on phagocytes produces opposite outcomes by potentiating and suppressing phagocytosis, respectively. Moreover, the Orion dosage is a key determinant of the sensitivity of phagocytes to PS exposed on neurons. Lastly, mutagenesis analyses show that the sequence motifs shared between Orion and human immunomodulatory proteins are important for Orion function. Thus, our results uncover a missing link in PS-mediated phagocytosis in and imply conserved mechanisms of phagocytosis of neurons.
Topics: Animals; Humans; Apoptosis; Chemokines; Drosophila; Drosophila Proteins; Neurons; Phagocytosis; Phosphatidylserines
PubMed: 37276397
DOI: 10.1073/pnas.2303392120 -
Frontiers in Immunology 2024Macrophages are the main component of the tumor microenvironment, which are differentiated from monocytes in the blood and play an important role in cancer development.... (Review)
Review
Macrophages are the main component of the tumor microenvironment, which are differentiated from monocytes in the blood and play an important role in cancer development. Tumor-associated macrophages (TAMs) can promote tumor growth, invasion, metastasis, and resistance to anti-programmed death receptor 1 therapy by regulating programmed cell death ligand 1 expression and interacting with other immune cells in the tumor microenvironment. However, when activated properly, macrophages can also play an anti-tumor role by enhancing the phagocytosis and cytotoxicity of tumor cells. TAM is associated with poor prognosis and drug resistance in patients treated with immunotherapy, indicating that macrophages are attractive targets for combined therapy in cancer treatment. Combination of targeting TAMs and immunotherapy overcomes the drug resistance and achieved excellent results in some cancers, which may be a promising strategy for cancer treatment in the future. Herein, we review the recent findings on the role of macrophages in tumor development, metastasis, and immunotherapy. We focus mainly on macrophage≥centered therapy, including strategies to deplete and reprogram TAMs, which represent the potential targets for improving tumor immunotherapy efficacy.
Topics: Humans; Macrophages; Neoplasms; Immunotherapy; Phagocytosis; Tumor Microenvironment
PubMed: 38605951
DOI: 10.3389/fimmu.2024.1381225 -
Biomolecules May 2023Age-related macular degeneration (AMD) causes vision loss in the elderly population. Dry AMD leads to the formation of Drusen, while wet AMD is characterized by cell... (Review)
Review
Age-related macular degeneration (AMD) causes vision loss in the elderly population. Dry AMD leads to the formation of Drusen, while wet AMD is characterized by cell proliferation and choroidal angiogenesis. The retinal pigment epithelium (RPE) plays a key role in AMD pathogenesis. In particular, helioreceptor renewal depends on outer segment phagocytosis of RPE cells, while RPE autophagy can protect cells from oxidative stress damage. However, when the oxidative stress burden is too high and homeostasis is disturbed, the phagocytosis and autophagy functions of RPE become damaged, leading to AMD development and progression. Hence, characterizing the roles of RPE cell phagocytosis and autophagy in the pathogenesis of AMD can inform the development of potential therapeutic targets to prevent irreversible RPE and photoreceptor cell death, thus protecting against AMD.
Topics: Aged; Humans; Phagocytosis; Autophagy; Macular Degeneration; Oxidative Stress; Epithelial Cells; Retinal Pigments
PubMed: 37371481
DOI: 10.3390/biom13060901 -
Current Opinion in Cell Biology Aug 2022Cells ingest large particles, such as bacteria, viruses, or apoptotic cells, via the process of phagocytosis, which involves formation of an actin-rich structure known... (Review)
Review
Cells ingest large particles, such as bacteria, viruses, or apoptotic cells, via the process of phagocytosis, which involves formation of an actin-rich structure known as the phagocytic cup. Phagocytic cup assembly and closure results from a concerted action of phagocytic receptors, regulators of actin polymerization, and myosin motors. Recent studies using advanced imaging approaches and biophysical techniques have revealed new information regarding phagocytic cup architecture, regulation of actin assembly, and the distribution, direction, and magnitude of the forces produced by the cytoskeletal elements that form the cup. These findings provide insights into the mechanisms leading to the assembly, expansion, and closure of phagocytic cups. The new data show that engulfment and internalization of phagocytic targets rely on several distinct yet complementary mechanisms that support the robust uptake of foreign objects and may be precisely tailored to the demands of specific phagocytic pathways.
Topics: Actins; Cell Membrane; Cytoskeleton; Phagocytes; Phagocytosis
PubMed: 35820329
DOI: 10.1016/j.ceb.2022.102112 -
Cells Sep 2021Macrophages maintain tissue homeostasis by phagocytosing and removing unwanted materials such as dead cells and cell debris. Microglia, the resident macrophages of the... (Review)
Review
Macrophages maintain tissue homeostasis by phagocytosing and removing unwanted materials such as dead cells and cell debris. Microglia, the resident macrophages of the central nervous system (CNS), are no exception. In addition, a series of recent studies have shown that microglia phagocytose the neuronal synapses that form the basis of neural circuit function. This discovery has spurred many neuroscientists to study microglia. Importantly, in the CNS parenchyma, not only microglia but also blood-derived monocytes, which essentially differentiate into macrophages after infiltration, exert phagocytic ability, making the study of phagocytosis in the CNS even more interesting and complex. In particular, in the diseased brain, the phagocytosis of tissue-damaging substances, such as myelin debris in multiple sclerosis (MS), has been shown to be carried out by both microglia and blood-derived monocytes. However, it remains largely unclear why blood-derived monocytes need to invade the parenchyma, where microglia are already abundant, to assist in phagocytosis. We will also discuss whether this phagocytosis can affect the fate of the phagocytosing cell itself as well as the substance being phagocytosed and the surrounding environment in addition to future research directions. In this review, we will introduce recent studies to answer a question that often arises when studying microglial phagocytosis: under what circumstances and to what extent blood-derived monocytes infiltrate the CNS and contribute to phagocytosis. In addition, the readers will learn how recent studies have experimentally distinguished between microglia and infiltrating monocytes. Finally, we aim to contribute to the progress of phagocytosis research by discussing the effects of phagocytosis on phagocytic cells.
Topics: Animals; Central Nervous System; Disease Models, Animal; Mice; Microglia; Monocytes; Phagocytosis
PubMed: 34685535
DOI: 10.3390/cells10102555 -
International Journal of Molecular... Feb 2022The retinal pigment epithelium (RPE) is a single layer of cells located between the choriocapillaris vessels and the light-sensitive photoreceptors in the outer retina.... (Review)
Review
The retinal pigment epithelium (RPE) is a single layer of cells located between the choriocapillaris vessels and the light-sensitive photoreceptors in the outer retina. The RPE performs physiological processes necessary for the maintenance and support of photoreceptors and visual function. Among the many functions performed by the RPE, the timing of the peak in phagocytic activity by the RPE of the photoreceptor outer segments that occurs 1-2 h. after the onset of light has captured the interest of many investigators and has thus been intensively studied. Several studies have shown that this burst in phagocytic activity by the RPE is under circadian control and is present in nocturnal and diurnal species and rod and cone photoreceptors. Previous investigations have demonstrated that a functional circadian clock exists within multiple retinal cell types and RPE cells. However, the anatomical location of the circadian controlling this activity is not clear. Experimental evidence indicates that the circadian clock, melatonin, dopamine, and integrin signaling play a key role in controlling this rhythm. A series of very recent studies report that the circadian clock in the RPE controls the daily peak in phagocytic activity. However, the loss of the burst in phagocytic activity after light onset does not result in photoreceptor or RPE deterioration during aging. In the current review, we summarized the current knowledge on the mechanism controlling this phenomenon and the physiological role of this peak.
Topics: Circadian Clocks; Circadian Rhythm; Phagocytosis; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium
PubMed: 35269840
DOI: 10.3390/ijms23052699 -
Medecine Sciences : M/S 2019Phagocytosis and macroautophagy, named here autophagy, are two essential mechanisms of lysosomal degradation of diverse cargos into membrane structures. Both mechanisms... (Review)
Review
Phagocytosis and macroautophagy, named here autophagy, are two essential mechanisms of lysosomal degradation of diverse cargos into membrane structures. Both mechanisms are involved in immune regulation and cell survival. However, phagocytosis triggers degradation of extracellular material whereas autophagy engulfs only cytoplasmic elements. Furthermore, activation and maturation of these two processes are different. LAP (LC3-associated phagocytosis) is a form of phagocytosis that uses components of the autophagy pathway. It can eliminate (i) pathogens, (ii) immune complexes, (iii) threatening neighbouring cells, dead or alive, and (iv) cell debris, such as POS (photoreceptor outer segment) and the midbody released at the end of mitosis. Cells have thus optimized their means of elimination of dangerous components by sharing some fundamental elements coming from the two main lysosomal degradation pathways.
Topics: Animals; Autophagy; Humans; Immune Evasion; Infections; Macrophages; Microtubule-Associated Proteins; Phagocytosis; Phagosomes
PubMed: 31532375
DOI: 10.1051/medsci/2019129 -
Frontiers in Immunology 2022Integrins are a large group of cell-surface proteins that are classified as transmembrane proteins. Integrins are classified into different types based on sequence... (Review)
Review
Integrins are a large group of cell-surface proteins that are classified as transmembrane proteins. Integrins are classified into different types based on sequence variations, leading to structural and functional diversity. They are broadly distributed in animals and have a wide range of biological functions such as cell-to-cell communication, intracellular cytoskeleton organization, cellular signaling, immune responses, etc. Integrins are among the most abundant cell surface proteins in insects, exhibiting their indispensability in insect physiology. Because of their critical biological involvement in physiological processes, they appear to be a novel target for designing effective pest control strategies. In the current literature review, we first discuss the discovery and expression responses of integrins against various types of pathogens. Secondly, we examine the specific biological roles of integrins in controlling microbial pathogens, such as phagocytosis, encapsulation, nodulation, immune signaling, and so on. Finally, we describe the possible uses of integrins to control agricultural insect pests.
Topics: Animals; Insecta; Integrins; Phagocytosis; Signal Transduction
PubMed: 35757717
DOI: 10.3389/fimmu.2022.906294 -
Frontiers in Endocrinology 2021The tissue microenvironment in the mouse pancreas has been shown to promote very different polarizations of resident macrophages with islet-resident macrophages...
The tissue microenvironment in the mouse pancreas has been shown to promote very different polarizations of resident macrophages with islet-resident macrophages displaying an inflammatory "M1" profile and macrophages in the exocrine tissue mostly displaying an alternatively activated "M2" profile. The impact of this polarization on tissue homeostasis and diabetes development is unclear. In this study, the ability of pancreas-resident macrophages to phagocyte bacterial and endogenous debris was investigated. Mouse endocrine and exocrine tissues were separated, and tissue-resident macrophages were isolated by magnetic immunolabeling. Isolated macrophages were subjected to flow cytometry for polarization markers and qPCR for phagocytosis-related genes. Functional investigations included phagocytosis and efferocytosis assays using pH-sensitive fluorescent bacterial particles and dead fluorescent neutrophils, respectively. Intravital confocal imaging of phagocytosis and efferocytosis in the pancreas was used to confirm findings . Gene expression analysis revealed no significant overall difference in expression of most phagocytosis-related genes in islet-resident vs. exocrine-resident macrophages included in the analysis. In this study, pancreas-resident macrophages were shown to differ in their ability to phagocyte bacterial and endogenous debris depending on their microenvironment. This difference in abilities may be one of the factors polarizing islet-resident macrophages to an inflammatory state since phagocytosis has been found to imprint macrophage heterogeneity. It remains unclear if this difference has any implications in the development of islet dysfunction or autoimmunity.
Topics: Animals; Apoptosis; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neutrophils; Pancreas; Phagocytosis
PubMed: 34113315
DOI: 10.3389/fendo.2021.606175