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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 -
Frontiers in Cellular Neuroscience 2022Galectin-3 (Gal-3; formally named MAC-2) is a β-galactoside-binding lectin. Various cell types produce Gal-3 under either normal conditions and/or pathological... (Review)
Review
Galectin-3 (Gal-3; formally named MAC-2) is a β-galactoside-binding lectin. Various cell types produce Gal-3 under either normal conditions and/or pathological conditions. Gal-3 can be present in cells' nuclei and cytoplasm, secreted from producing cells, and associated with cells' plasma membranes. This review focuses on how Gal-3 controls phagocytosis and macropinocytosis. Intracellular and extracellular Gal-3 promotes the phagocytosis of phagocytic targets/cargo (e.g., tissue debris and apoptotic cells) in "professional phagocytes" (e.g., microglia and macrophages) and "non-professional phagocytes" (e.g., Schwann cells and astrocytes). Intracellularly, Gal-3 promotes phagocytosis by controlling the "eat me" signaling pathways that phagocytic receptors generate, directing the cytoskeleton to produce the mechanical forces that drive the structural changes on which phagocytosis depends, protrusion and then retraction of filopodia and lamellipodia as they, respectively, engulf and then internalize phagocytic targets. Extracellularly, Gal-3 promotes phagocytosis by functioning as an opsonin, linking phagocytic targets to phagocytic receptors, activating them to generate the "eat me" signaling pathways. Macropinocytosis is a non-selective endocytic mechanism that various cells use to internalize the bulk of extracellular fluid and included materials/cargo (e.g., dissolved nutrients, proteins, and pathogens). Extracellular and intracellular Gal-3 control macropinocytosis in some types of cancer. Phagocytosed and macropinocytosed targets/cargo that reach lysosomes for degradation may rupture lysosomal membranes. Damaged lysosomal membranes undergo either repair or removal by selective autophagy (i.e., lysophagy) that intracellular Gal-3 controls.
PubMed: 36274989
DOI: 10.3389/fncel.2022.949079 -
Advanced Drug Delivery Reviews Sep 2022The propensity of the hepatic macrophages (Kupffer cells) to rapidly intercept particulate materials from the blood has been frustrating in redirecting intravenously... (Review)
Review
The propensity of the hepatic macrophages (Kupffer cells) to rapidly intercept particulate materials from the blood has been frustrating in redirecting intravenously injected nanomedicines to pathological sites in sufficient quantities to exert appropriate pharmacological effect. The development of long circulating nanoparticles has offered unprecedented opportunities for controlled drug release within vasculature and for drug delivery to sites other than Kupffer cells. These developments were based on mechanistic understanding of complex and integrated body's defences against intruders as well as translation of protective strategies developed by the body's own cells and virulent pathogens against immune attack. Thanks to interdisciplinary and integrated approaches, numerous organic and inorganic nanoparticles with long circulating properties have become available. By long circulation we mean particles that remain in the blood for periods of hours rather than minutes, but blood longevity must be tuned in accordance with therapeutic needs. Here, we provide a brief history of these efforts and highlight important lessons learned in camouflaging nanoparticles with strategies that avoid rapid interception by Kupffer cells.
Topics: Drug Delivery Systems; Humans; Kupffer Cells; Nanomedicine; Nanoparticles
PubMed: 35798129
DOI: 10.1016/j.addr.2022.114396 -
Clinical and Vaccine Immunology : CVI Jun 2017Immunity to pneumococcal infections is impaired in older people, and current vaccines are poorly protective against pneumococcal disease in this population. Naturally... (Review)
Review
Immunity to pneumococcal infections is impaired in older people, and current vaccines are poorly protective against pneumococcal disease in this population. Naturally acquired immunity to pneumococcal capsular polysaccharides develops during childhood and is robust in young adults but deteriorates with advanced age. In particular, antibody levels and function are reduced in older people. Pneumococcal vaccines are recommended for people >65 years old. However, the benefits of polysaccharide and protein-conjugated vaccines in this population are small, because of both serotype replacement and incomplete protection against vaccine serotype pneumococcal disease. In this review, we overview the immune mechanisms by which naturally acquired and vaccine-induced pneumococcal capsular polysaccharide immunity declines with age, including altered colonization dynamics, reduced opsonic activity of antibodies (particularly IgM), and impaired mucosal immunity.
Topics: Age Factors; Aged; Aged, 80 and over; Antibodies, Bacterial; Bacterial Capsules; Carrier State; Humans; Immunity, Mucosal; Opsonin Proteins; Pneumococcal Infections; Streptococcus pneumoniae
PubMed: 28424198
DOI: 10.1128/CVI.00004-17 -
Frontiers in Immunology 2017Tunicates are the closest relatives of vertebrates, and their peculiar phylogenetic position explains the increasing interest toward tunicate immunobiology. They are... (Review)
Review
Tunicates are the closest relatives of vertebrates, and their peculiar phylogenetic position explains the increasing interest toward tunicate immunobiology. They are filter-feeding organisms, and this greatly influences their defense strategies. The majority of the studies on tunicate immunity were carried out in ascidians. The tunic acts as a first barrier against pathogens and parasites. In addition, the oral siphon and the pharynx represent two major, highly vascularized, immune organs, where circulating hemocytes can sense non-self material and trigger immune responses that, usually, lead to inflammation and phagocytosis. Inflammation involves the recruitment of circulating cytotoxic, phenoloxidase (PO)-containing cells in the infected area, where they degranulate as a consequence of non-self recognition and release cytokines, complement factors, and the enzyme PO. The latter, acting on polyphenol substrata, produces cytotoxic quinones, which polymerize to melanin, and reactive oxygen species, which induce oxidative stress. Both the alternative and the lectin pathways of complement activation converge to activate C3: C3a and C3b are involved in the recruitment of hemocytes and in the opsonization of foreign materials, respectively. The interaction of circulating professional phagocytes with potentially pathogenic foreign material can be direct or mediated by opsonins, either complement dependent or complement independent. Together with cytotoxic cells, phagocytes are active in the encapsulation of large materials. Cells involved in immune responses, collectively called immunocytes, represent a large fraction of hemocytes, and the presence of a cross talk between cytotoxic cells and phagocytes, mediated by secreted humoral factors, was reported. Lectins play a pivotal role as pattern-recognition receptors and opsonizing agents. In addition, variable region-containing chitin-binding proteins, identified in the solitary ascidian , control the settlement and colonization of bacteria in the gut.
PubMed: 28649250
DOI: 10.3389/fimmu.2017.00674 -
Frontiers in Immunology 2020Understanding the effects mediated by a set of nanoparticle (NP)-bound host biomolecules, often indicated with the term of , is essential in nanomedicine,... (Review)
Review
Understanding the effects mediated by a set of nanoparticle (NP)-bound host biomolecules, often indicated with the term of , is essential in nanomedicine, nanopharmacology, and nanotoxicology. Among the NP-adsorbed , some factors mediate cell binding, endocytosis, and clearing by macrophages and other phagocytes (opsonins), while some others display few affinities for the cell surface (dysopsonins). The functional mapping of opsonins and dysopsonins is instrumental to design long-circulating and nanotoxicologically safe next-generation nanotheranostics. In this review, we critically analyze functional data identifying specific proteins with opsonin or dysopsonin properties. Special attention is dedicated to the following: (1) the simplicity or complexity of the NP proteome and its modulation, (2) the role of specific host proteins in mediating the stealth properties of uncoated or polymer-coated NPs, and (3) the ability of the innate immune system, and, in particular, of the complement proteins, to mediate NP clearance by phagocytes. Emerging species-specific peculiarities, differentiating humans from preclinical animal models (the murine especially), are highlighted throughout this overview. The operative definition of opsonin and dysopsonin and the measurement schemes to assess their efficacy is critically re-examined. This provides a shared and unbiased approach useful for NP opsonin and dysopsonin systematic identification.
Topics: Animals; Carrier Proteins; Complement System Proteins; Guidelines as Topic; Humans; Immunomodulation; Macrophages; Nanoparticles; Opsonin Proteins; Phagocytes; Protein Binding; Proteome; Theranostic Nanomedicine
PubMed: 33154748
DOI: 10.3389/fimmu.2020.567365 -
International Journal of Molecular... Feb 2018The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM), and to a... (Review)
Review
The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM), and to a lesser degree, as coordinators of leukocyte adhesion to the endothelium. These canonical activities are indispensable; however, there is also a wide variety of integrin functions mediated by non-ECM ligands that transcend the traditional roles of integrins. Some of these unorthodox roles involve cell-cell interactions and are engaged to support immune functions such as leukocyte transmigration, recognition of opsonization factors, and stimulation of neutrophil extracellular traps. Other cell-cell interactions mediated by integrins include hematopoietic stem cell and tumor cell homing to target tissues. Integrins also serve as cell-surface receptors for various growth factors, hormones, and small molecules. Interestingly, integrins have also been exploited by a wide variety of organisms including viruses and bacteria to support infectious activities such as cellular adhesion and/or cellular internalization. Additionally, the disruption of integrin function through the use of soluble integrin ligands is a common strategy adopted by several parasites in order to inhibit blood clotting during hematophagy, or by venomous snakes to kill prey. In this review, we strive to go beyond the matrix and summarize non-ECM ligands that interact with integrins in order to highlight these non-traditional functions of integrins.
Topics: Animals; Cell Communication; Cell Movement; Endothelium; Extracellular Matrix; Extracellular Traps; Gene Expression Regulation; Hormones; Humans; Integrins; Intercellular Signaling Peptides and Proteins; Leukocytes; Ligands; Opsonin Proteins; Protein Binding; Signal Transduction; Snake Venoms; Viral Proteins
PubMed: 29393909
DOI: 10.3390/ijms19020449 -
Frontiers in Cellular Neuroscience 2020Microglia are brain macrophages that mediate neuroinflammation and contribute to and protect against neurodegeneration. The terminal sugar residue of all glycoproteins... (Review)
Review
Microglia are brain macrophages that mediate neuroinflammation and contribute to and protect against neurodegeneration. The terminal sugar residue of all glycoproteins and glycolipids on the surface of mammalian cells is normally sialic acid, and addition of this negatively charged residue is known as "sialylation," whereas removal by sialidases is known as "desialylation." High sialylation of the neuronal cell surface inhibits microglial phagocytosis of such neurons, via: (i) activating sialic acid receptors (Siglecs) on microglia that inhibit phagocytosis and (ii) inhibiting binding of opsonins C1q, C3, and galectin-3. Microglial sialylation inhibits inflammatory activation of microglia via: (i) activating Siglec receptors CD22 and CD33 on microglia that inhibit phagocytosis and (ii) inhibiting Toll-like receptor 4 (TLR4), complement receptor 3 (CR3), and other microglial receptors. When activated, microglia release a sialidase activity that desialylates both microglia and neurons, activating the microglia and rendering the neurons susceptible to phagocytosis. Activated microglia also release galectin-3 (Gal-3), which: (i) further activates microglia via binding to TLR4 and TREM2, (ii) binds to desialylated neurons opsonizing them for phagocytosis via Mer tyrosine kinase, and (iii) promotes Aβ aggregation and toxicity . Gal-3 and desialylation may increase in a variety of brain pathologies. Thus, Gal-3 and sialidases are potential treatment targets to prevent neuroinflammation and neurodegeneration.
PubMed: 32581723
DOI: 10.3389/fncel.2020.00162 -
Clinical and Experimental Immunology Feb 2016Active complement mediators play a key role in graft-versus-host diseases, but little attention has been given to the angiogenic balance and complement modulation during... (Review)
Review
Active complement mediators play a key role in graft-versus-host diseases, but little attention has been given to the angiogenic balance and complement modulation during allograft acceptance. The complement cascade releases the powerful proinflammatory mediators C3a and C5a anaphylatoxins, C3b, C5b opsonins and terminal membrane attack complex into tissues, which are deleterious if unchecked. Blocking complement mediators has been considered to be a promising approach in the modern drug discovery plan, and a significant number of therapeutic alternatives have been developed to dampen complement activation and protect host cells. Numerous immune cells, especially macrophages, develop both anaphylatoxin and opsonin receptors on their cell surface and their binding affects the macrophage phenotype and their angiogenic properties. This review discusses the mechanism that complement contributes to angiogenic injury, and the development of future therapeutic targets by antagonizing activated complement mediators to preserve microvasculature in rejecting the transplanted organ.
Topics: Complement Activation; Complement Membrane Attack Complex; Complement System Proteins; Graft Rejection; Graft vs Host Disease; Humans; Macrophages; Microvessels; Molecular Targeted Therapy; Neovascularization, Physiologic; Transplants
PubMed: 26404106
DOI: 10.1111/cei.12713