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Biomolecules Jul 2021Neutrophil elastase (NE) is a major inflammatory protease released by neutrophils and is present in the airways of patients with cystic fibrosis (CF), chronic... (Review)
Review
Neutrophil elastase (NE) is a major inflammatory protease released by neutrophils and is present in the airways of patients with cystic fibrosis (CF), chronic obstructive pulmonary disease, non-CF bronchiectasis, and bronchopulmonary dysplasia. Although NE facilitates leukocyte transmigration to the site of infection and is required for clearance of Gram-negative bacteria, it also activates inflammation when released into the airway milieu in chronic inflammatory airway diseases. NE exposure induces airway remodeling with increased mucin expression and secretion and impaired ciliary motility. NE interrupts epithelial repair by promoting cellular apoptosis and senescence and it activates inflammation directly by increasing cytokine expression and release, and indirectly by triggering extracellular trap release and exosome release, which magnify protease activity and inflammation in the airway. NE inhibits innate immune function by digesting opsonins and opsonin receptors, degrading innate immune proteins such as lactoferrin, and inhibiting macrophage phagocytosis. Importantly, NE-directed therapies have not yet been effective in preventing the pathologic sequelae of NE exposure, but new therapies are being developed that offer both direct antiprotease activity and multifunctional anti-inflammatory properties.
Topics: Animals; Chronic Disease; Humans; Leukocyte Elastase; Lung; Lung Diseases; Neutrophils
PubMed: 34439732
DOI: 10.3390/biom11081065 -
Immunological Reviews Jan 2023C3 is the central effector molecule of the complement system, mediating its multiple functions through different binding sites and their corresponding receptors. We will... (Review)
Review
C3 is the central effector molecule of the complement system, mediating its multiple functions through different binding sites and their corresponding receptors. We will introduce the C3 forms (native C3, C3 [H O], and intracellular C3), the C3 fragments C3a, C3b, iC3b, and C3dg/C3d, and the C3 expression sites. To highlight the important role that C3 plays in human biological processes, we will give an overview of the diseases linked to C3 deficiency and to uncontrolled C3 activation. Next, we will present a structural description of C3 activation and of the C3 fragments generated by complement regulation. We will proceed by describing the C3a interaction with the anaphylatoxin receptor, followed by the interactions of opsonins (C3b, iC3b, and C3dg/C3d) with complement receptors, divided into two groups: receptors bearing complement regulatory functions and the effector receptors without complement regulatory activity. We outline the molecular architecture of the receptors, their binding sites on the C3 activation fragments, the cells expressing them, the diversity of their functions, and recent advances. With this review, we aim to give an up-to-date analysis of the processes triggered by C3 activation fragments on different cell types in health and disease contexts.
Topics: Humans; Complement C3; Complement C3b; Receptors, Complement; Binding Sites; Complement Activation
PubMed: 36271889
DOI: 10.1111/imr.13147 -
Frontiers in Immunology 2020Phagocytosis is a cellular process for ingesting and eliminating particles larger than 0.5 μm in diameter, including microorganisms, foreign substances, and apoptotic... (Review)
Review
Phagocytosis is a cellular process for ingesting and eliminating particles larger than 0.5 μm in diameter, including microorganisms, foreign substances, and apoptotic cells. Phagocytosis is found in many types of cells and it is, in consequence an essential process for tissue homeostasis. However, only specialized cells termed professional phagocytes accomplish phagocytosis with high efficiency. Macrophages, neutrophils, monocytes, dendritic cells, and osteoclasts are among these dedicated cells. These professional phagocytes express several phagocytic receptors that activate signaling pathways resulting in phagocytosis. The process of phagocytosis involves several phases: i) detection of the particle to be ingested, ii) activation of the internalization process, iii) formation of a specialized vacuole called phagosome, and iv) maturation of the phagosome to transform it into a phagolysosome. In this review, we present a general view of our current understanding on cells, phagocytic receptors and phases involved in phagocytosis.
Topics: Apoptosis; Humans; Models, Immunological; Pathogen-Associated Molecular Pattern Molecules; Phagocytes; Phagocytosis; Phagosomes; Receptors, Complement; Receptors, IgG; Receptors, Immunologic; Receptors, Pattern Recognition; Signal Transduction
PubMed: 32582172
DOI: 10.3389/fimmu.2020.01066 -
Developmental and Comparative Immunology Sep 2021Melanin production from different types of phenoloxidases (POs) confers immunity from a variety of pathogens ranging from viruses and microorganisms to parasites. The... (Review)
Review
Melanin production from different types of phenoloxidases (POs) confers immunity from a variety of pathogens ranging from viruses and microorganisms to parasites. The arthropod proPO expresses a variety of activities including cytokine, opsonin and microbiocidal activities independent of and even without melanin production. Proteolytic processing of proPO and its activating enzyme gives rise to several peptide fragments with a variety of separate activities in a process reminiscent of vertebrate complement system activation although proPO bears no sequence similarity to vertebrate complement factors. Pathogens influence proPO activation and thereby what types of immune effects that will be produced. An increasing number of specialised pathogens - from parasites to viruses - have been identified who can synthesise compounds specifically aimed at the proPO-system. In invertebrates outside the arthropods phylogenetically unrelated POs are participating in melanization reactions obviously aimed at intruders and/or aberrant tissues.
Topics: Animals; Arthropods; Bacteria; Cell Proliferation; Enzyme Activation; Enzyme Precursors; Fungi; Hemocytes; Immunity, Innate; Melanins; Monophenol Monooxygenase; Receptors, Pattern Recognition; Viruses
PubMed: 33857469
DOI: 10.1016/j.dci.2021.104098 -
Frontiers in Immunology 2020Phagocytosis is an ancient, highly conserved process in all multicellular organisms, through which the host can protect itself against invading microorganisms and... (Review)
Review
Phagocytosis is an ancient, highly conserved process in all multicellular organisms, through which the host can protect itself against invading microorganisms and environmental particles, as well as remove self-apoptotic cells/cell debris to maintain tissue homeostasis. In crustacean, phagocytosis by hemocyte has also been well-recognized as a crucial defense mechanism for the host against infectious agents such as bacteria and viruses. In this review, we summarized the current knowledge of hemocyte-mediated phagocytosis, in particular focusing on the related receptors for recognition and internalization of pathogens as well as the downstream signal pathways and intracellular regulators involved in the process of hemocyte phagocytosis. We attempted to gain a deeper understanding of the phagocytic mechanism of different hemocytes and their contribution to the host defense immunity in crustaceans.
Topics: Animals; Cell Adhesion Molecules; Crustacea; Hemocytes; Host-Pathogen Interactions; Immunity, Innate; Lectins; Opsonin Proteins; Phagocytes; Phagocytosis; Phagosomes; Pore Forming Cytotoxic Proteins; Receptors, Pattern Recognition; Receptors, Scavenger; Signal Transduction
PubMed: 32194551
DOI: 10.3389/fimmu.2020.00268 -
Biochemical Society Transactions Oct 2022Phagocytosis triggered by the phospholipid phosphatidylserine (PS) is key for the removal of apoptotic cells in development, tissue homeostasis and infection. Modulation... (Review)
Review
Phagocytosis triggered by the phospholipid phosphatidylserine (PS) is key for the removal of apoptotic cells in development, tissue homeostasis and infection. Modulation of PS-mediated phagocytosis is an attractive target for therapeutic intervention in the context of atherosclerosis, neurodegenerative disease, and cancer. Whereas the mechanisms of target recognition, lipid and protein signalling, and cytoskeletal remodelling in opsonin-driven modes of phagocytosis are increasingly well understood, PS-mediated phagocytosis has remained more elusive. This is partially due to the involvement of a multitude of receptors with at least some redundancy in functioning, which complicates dissecting their contributions and results in complex downstream signalling networks. This review focusses on the receptors involved in PS-recognition, the signalling cascades that connect receptors to cytoskeletal remodelling required for phagocytosis, and recent progress in our understanding of how phagocytic cup formation is coordinated during PS-mediated phagocytosis.
Topics: Humans; Phosphatidylserines; Neurodegenerative Diseases; Apoptosis; Phagocytosis; Signal Transduction
PubMed: 36281986
DOI: 10.1042/BST20211254 -
Frontiers in Immunology 2020
Topics: Animals; Humans; Phagocytosis
PubMed: 33072133
DOI: 10.3389/fimmu.2020.586918 -
Medical Hypotheses Jan 2021We hypothesize that polycations, such as nuclear histones, released by neutrophils COVID-19 aggravate COVID-19 by multiple mechanisms: (A) Neutralization of the... (Review)
Review
We hypothesize that polycations, such as nuclear histones, released by neutrophils COVID-19 aggravate COVID-19 by multiple mechanisms: (A) Neutralization of the electrostatic repulsion between the virus particles and the cell membrane, thereby enhancing receptor-mediated entry. (B) Binding to the virus particles, thereby inducing opsonin-mediated endocytosis. (C) Adding to the cytotoxicity, in conjunction with oxidants, cytokines and other pro-inflammatory substances secreted by cells of the innate immunity system. These effects may be alleviated by the administration of negatively charged polyanions such as heparins and heparinoids.
Topics: Antiviral Agents; COVID-19; Endocytosis; Heparin; Histones; Humans; Immunity, Innate; Models, Biological; Neutrophils; Pandemics; Polyelectrolytes; SARS-CoV-2; Static Electricity; Virus Internalization; COVID-19 Drug Treatment
PubMed: 33412501
DOI: 10.1016/j.mehy.2020.110470