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Current Opinion in Pulmonary Medicine Jan 2020Asthma is a chronic inflammatory disease in which changes in macrophage polarization have been shown to contribute to the pathogenesis. The present review discusses the... (Review)
Review
PURPOSE OF REVIEW
Asthma is a chronic inflammatory disease in which changes in macrophage polarization have been shown to contribute to the pathogenesis. The present review discusses the contribution of changes in macrophage function to asthma related to polarization changes and elaborates on possible therapeutic strategies targeting macrophage function and polarization.
RECENT FINDINGS
Macrophage function alterations were shown to contribute to asthma pathology in several ways. One is by impaired phagocytosis and efferocytosis. Another is by changing inflammation, by altered (anti)inflammatory cytokine production and induction of the inflammasome. Finally, macrophages can contribute to remodeling in asthma, although little evidence is present in humans yet.Novel therapeutic strategies targeting macrophages include dampening inflammation by changing polarization or by inhibiting the NLRP3 inflammasome, and by targeting efferocytosis. However, many of these studies were performed in animal models leaving their translation to the clinic for future research.
SUMMARY
The present review emphasizes the contribution of altered macrophage function to asthma, gives insight in possible new therapeutic strategies targeting macrophages, and indicates which knowledge gaps remain open.
Topics: Animals; Asthma; Cell Polarity; Humans; Inflammation; Macrophages, Alveolar; Phagocytosis
PubMed: 31703000
DOI: 10.1097/MCP.0000000000000647 -
Current Opinion in Cell Biology Dec 2021Neuronal-immune interactions are known to play crucial roles in brain development and homoeostasis. Of great relevance in this context are microglia, brain macrophages... (Review)
Review
Neuronal-immune interactions are known to play crucial roles in brain development and homoeostasis. Of great relevance in this context are microglia, brain macrophages that phagocytose neurons that die during development, and many neurological disorders. Single-cell RNA sequencing methods have significantly advanced our understanding of microglial heterogeneity and transcriptional response to environmental changes. Here, we review recent work showing how microglia adopt a similar molecular signature during development and disease characterised by the expression of genes linked to phagocytosis and lipid uptake and metabolism. These studies show that in many neurodegenerative conditions, microglia accumulate cholesterols and lipid-rich debris, pointing to lipid processing and transport as promising targets for developing new therapeutical treatments against neurodegenerative disorders.
Topics: Brain; Macrophages; Microglia; Neurons; Phagocytosis; Weight Prejudice
PubMed: 34455405
DOI: 10.1016/j.ceb.2021.07.007 -
Annual Review of Chemical and... Jun 2021When attempting to propagate infections, bacterial pathogens encounter phagocytes that encase them in vacuoles called phagosomes. Within phagosomes, bacteria are... (Review)
Review
When attempting to propagate infections, bacterial pathogens encounter phagocytes that encase them in vacuoles called phagosomes. Within phagosomes, bacteria are bombarded with a plethora of stresses that often lead to their demise. However, pathogens have evolved numerous strategies to counter those host defenses and facilitate survival. Given the importance of phagosome-bacteria interactions to infection outcomes, they represent a collection of targets that are of interest for next-generation antibacterials. To facilitate such therapies, different approaches can be employed to increase understanding of phagosome-bacteria interactions, and these can be classified broadly as top down (starting from intact systems and breaking down the importance of different parts) or bottom up (developing a knowledge base on simplified systems and progressively increasing complexity). Here we review knowledge of phagosomal compositions and bacterial survival tactics useful for bottom-up approaches, which are particularly relevant for the application of reaction engineering to quantify and predict the time evolution of biochemical species in these death-dealing vacuoles. Further, we highlight how understanding in this area can be built up through the combination of immunology, microbiology, and engineering.
Topics: Bacteria; Phagocytosis; Phagosomes
PubMed: 33781082
DOI: 10.1146/annurev-chembioeng-090920-015024 -
Sub-cellular Biochemistry 2022Phagocytes play critical roles in the maintenance of organismal homeostasis and immunity. Central to their role is their ability to take up and process exogenous...
Phagocytes play critical roles in the maintenance of organismal homeostasis and immunity. Central to their role is their ability to take up and process exogenous material via the related processes of phagocytosis and macropinocytosis. The mechanisms and functions underlying macropinocytosis have remained severely understudied relative to phagocytosis. In recent years, however, there has been a renaissance in macropinocytosis research. Phagocytes can engage in various forms of macropinocytosis including an "induced" form and a "constitutive" form. This chapter, however, will focus on constitutive macropinocytosis and its role in the maintenance of immunity. Functions previously attributed to macropinocytosis, including antigen presentation and immune surveillance, will be revisited in light of recent revelations and emerging concepts will be highlighted.
Topics: Antigen Presentation; Homeostasis; Phagocytes; Phagocytosis; Pinocytosis
PubMed: 35378705
DOI: 10.1007/978-3-030-94004-1_6 -
Sheng Li Xue Bao : [Acta Physiologica... Apr 2022With the acceleration of the aging society, neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have become a rapidly growing... (Review)
Review
With the acceleration of the aging society, neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have become a rapidly growing global health crisis. Recent studies have indicated that microglia-neuron interactions are critical for maintaining homeostasis of the central nervous system. Genome-Wide Association Studies and brain imaging studies have suggested that microglia are activated in early stage of neurodegenerative diseases. Microglia are specialized phagocytes in the brain. The discovery of a new phagocytic pathway, trogocytosis, suggests that there is a close interaction between microglia and surviving neurons. In this review, we summarize the important roles of microglia in neurodegenerative diseases, and further analyze the functions and molecular mechanisms of microglia phagocytosis and trogocytosis.
Topics: Alzheimer Disease; Genome-Wide Association Study; Humans; Microglia; Neurodegenerative Diseases; Phagocytosis
PubMed: 35503076
DOI: No ID Found -
Pharmacology & Therapeutics Jan 2022Cell death and the clearance of apoptotic cells are tightly regulated by various signaling molecules in order to maintain physiological tissue function and homeostasis.... (Review)
Review
Cell death and the clearance of apoptotic cells are tightly regulated by various signaling molecules in order to maintain physiological tissue function and homeostasis. The phagocytic removal of apoptotic cells is known as the process of efferocytosis, and abnormal efferocytosis is linked to various health complications and diseases, such as cardiovascular disease, inflammatory diseases, and autoimmune diseases. During efferocytosis, phagocytic cells and/or apoptotic cells release signals, such as "find me" and "eat me" signals, to stimulate the phagocytic engulfment of apoptotic cells. Primary phagocytic cells are macrophages and dendritic cells; however, more recently, other neighboring cell types have also been shown to exhibit phagocytic character, including endothelial cells and fibroblasts, although they are comparatively slower in clearing dead cells. In this review, we focus on macrophage efferocytosis of vascular cells, such as endothelial cells, smooth muscle cells, fibroblasts, and pericytes, and its relation to the progression and development of cardiovascular disease. We also highlight the role of efferocytosis-related molecules and their contribution to the maintenance of vascular homeostasis.
Topics: Apoptosis; Cardiovascular Diseases; Endothelial Cells; Humans; Macrophages; Phagocytosis
PubMed: 34171333
DOI: 10.1016/j.pharmthera.2021.107919 -
Genes & Genomics Sep 2020One of the key features of the plasma membrane is the asymmetrical distribution of phospholipids across it. Especially, phosphatidylserine (PS) exclusively locates on... (Review)
Review
One of the key features of the plasma membrane is the asymmetrical distribution of phospholipids across it. Especially, phosphatidylserine (PS) exclusively locates on its inner leaflet. Thus, the exposure of PS on the surface of cells could function as a signal initiating various cellular processes such as phagocytosis of apoptotic cells called efferocytosis, blood clotting, muscle formation, and viral entry. Indeed, PS on apoptotic cells stimulates phagocytes to engulf them and functions as an essential ligand for efferocytosis. Due to the importance of PS in efferocytosis, the existence of the PS receptor had been conceived. However, the PS receptor had not been revealed for a long time. Thus, the first identification of the PS receptor was significant excitement. Tim-4, a member of the T cell immunoglobulin and mucin domain containing family of genes, was one of PS receptors which first identified and received the greatest attention due to its expression in macrophages and relevance to autoimmune and allergic diseases. This review will serve to provide a comprehensive overview of Tim proteins as PS receptors.
Topics: Apoptosis; Humans; Macrophages; Membrane Proteins; Phagocytosis; Phosphatidylserines; Receptors, Cell Surface; Signal Transduction
PubMed: 32648232
DOI: 10.1007/s13258-020-00969-x -
International Journal of Molecular... Feb 2023Phagocytosis is one of the most polarised of all cellular activities. Both the stimulus (the target for phagocytosis) and the response (its internalisation) are focussed... (Review)
Review
Phagocytosis is one of the most polarised of all cellular activities. Both the stimulus (the target for phagocytosis) and the response (its internalisation) are focussed at just one part of the cell. At the locus, and this locus alone, pseudopodia form a phagocytic cup around the particle, the cytoskeleton is rearranged, the plasma membrane is reorganised, and a new internal organelle, the phagosome, is formed. The effect of signals from the stimulus must, thus, both be complex and yet be restricted in space and time to enable an effective focussed response. While many aspects of phagocytosis are being uncovered, the mechanism for the restriction of signalling or the effects of signalling remains obscure. In this review, the details of the problem of restricting chemical intracellular signalling are presented, with a focus on diffusion into the cytosol and of signalling lipids along the plasma membrane. The possible ways in which simple diffusion is overcome so that the restriction of signalling and effective phagocytosis can be achieved are discussed in the light of recent advances in imaging, biophysics, and cell biochemistry which together are providing new insights into this area.
Topics: Phagocytosis; Phagosomes; Pseudopodia; Cytoskeleton; Cytosol
PubMed: 36769146
DOI: 10.3390/ijms24032825 -
Journal of Materials Chemistry. B Mar 2020A broad range of investigation methods and frameworks are currently used to throughly study the elasticity of various types of micro/nanoparticles (MNPs) with different... (Review)
Review
A broad range of investigation methods and frameworks are currently used to throughly study the elasticity of various types of micro/nanoparticles (MNPs) with different properties and to explore the effect of such properties on their interactions with biological species. Specifically, the elasticity of MNPs serves as a key influencing factor with respect to important aspects of phagocytosis, such as the clathrin-mediated phagocytosis, caveolae-mediated phagocytosis, macropinocytosis, and cell membrane fusion. Achieving a clear understanding of the relationships that exist between the elasticity of MNPs and their phagocytic processes is essential to improve their performance in drug delivery, which is related to aspects such as circulation lifetime in blood, accumulation time in tissues, and resistance to metabolism. Resolving such aspects is very challenging, and related efforts require using the right tools/methods, which are not always easy to identify. This review aims to facilitate this by summarizing and comparing different cell phagocytosis pathways, while considering various MNPs exhibiting different elastic properties, shape change capabilities, and their effect on cellular uptake. We conduct an overview of the advantages exhibited by different MNPs with respect to both in vitro and in vivo delivery, taking computational simulation analysis and experimental results into account. This study will provide a guide for how to investigate various types of MNPs in terms of their elastic properties, together with their biomedical effects that rely on phagocytosis.
Topics: Drug Delivery Systems; Elasticity; Molecular Dynamics Simulation; Nanoparticles; Particle Size; Phagocytosis; Surface Properties
PubMed: 32100802
DOI: 10.1039/c9tb02902h -
Annual Review of Cell and Developmental... Oct 2021Recent observations indicate that, rather than being an all-or-none response, phagocytosis is finely tuned by a host of developmental and environmental factors. The...
Recent observations indicate that, rather than being an all-or-none response, phagocytosis is finely tuned by a host of developmental and environmental factors. The expression of key phagocytic determinants is regulated via transcriptional and epigenetic means that confer memory on the process. Membrane traffic, the cytoskeleton, and inside-out signaling control the activation of phagocytic receptors and their ability to access their targets. An exquisite extra layer of complexity is introduced by the coexistence of distinct "eat-me" and "don't-eat-me" signals on targets and of corresponding "eat" and "don't-eat" receptors on the phagocyte surface. Moreover, assorted physical barriers constitute "don't-come-close-to-me" hurdles that obstruct the engagement of ligands by receptors. The expression, mobility, and accessibility of all these determinants can be modulated, conferring extreme plasticity on phagocytosis and providing attractive targets for therapeutic intervention in cancer, atherosclerosis, and dementia.
Topics: Humans; Neoplasms; Phagocytes; Phagocytosis; Plastics; Signal Transduction
PubMed: 34152790
DOI: 10.1146/annurev-cellbio-120219-055903