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Journal of Controlled Release :... Jul 2019Liposome as a revolutionizing carrier, has exhibited favorable aspects in drug delivery. However, there are numerous challenges affecting its effectiveness.... (Review)
Review
Liposome as a revolutionizing carrier, has exhibited favorable aspects in drug delivery. However, there are numerous challenges affecting its effectiveness. Hypersensitivity, accelerated blood clearance, opsonization, uptake by reticulo-endothelial system, and also immune suppression are known as the dominant manifestations of immune-related effects. They may cause failure to achieve the proof of regulatory approvals. In this review, liposome challenges in biologic environment have been discussed. Moreover, opsonization and liposome interactions with innate and acquired immune system have been investigated. Immune system elements including the corresponding receptors and cells were reviewed in this regard. By exploring immune related interactions of the liposome, it could be possible for the formulators to be aware of the immune related interactions of the administered liposomal formulation. On the other hand, immune targeted liposomes for immunotherapy and vaccination purposes could also be developed.
Topics: Animals; Drug Delivery Systems; Humans; Immune System; Immunity; Immunotherapy; Liposomes
PubMed: 31121278
DOI: 10.1016/j.jconrel.2019.05.030 -
Advances in Experimental Medicine and... 2020Collectins are collagen-containing C-type (calcium-dependent) lectins which are important pathogen pattern recognising innate immune molecules. Their primary structure... (Review)
Review
Collectins are collagen-containing C-type (calcium-dependent) lectins which are important pathogen pattern recognising innate immune molecules. Their primary structure is characterised by an N-terminal, triple-helical collagenous region made up of Gly-X-Y repeats, an a-helical coiled-coil trimerising neck region, and a C-terminal C-type lectin or carbohydrate recognition domain (CRD). Further oligomerisation of this primary structure can give rise to more complex and multimeric structures that can be seen under electron microscope. Collectins can be found in serum as well as in a range of tissues at the mucosal surfaces. Mannanbinding lectin can activate the complement system while other members of the collectin family are extremely versatile in recognising a diverse range of pathogens via their CRDs and bring about effector functions designed at the clearance of invading pathogens. These mechanisms include opsonisation, enhancement of phagocytosis, triggering superoxidative burst and nitric oxide production. Collectins can also potentiate the adaptive immune response via antigen presenting cells such as macrophages and dendritic cells through modulation of cytokines and chemokines, thus they can act as a link between innate and adaptive immunity. This chapter describes the structure-function relationships of collectins, their diverse functions, and their interaction with viruses, bacteria, fungi and parasites.
Topics: Adaptive Immunity; Animals; Bacteria; Collectins; Fungi; Humans; Immunity, Innate; Parasites; Viruses
PubMed: 32152944
DOI: 10.1007/978-981-15-1580-4_4 -
Immunological Reviews Mar 2023Tumor-targeting monoclonal antibodies are available for a number of cancer cell types (over)expressing the corresponding tumor antigens. Such antibodies can limit tumor... (Review)
Review
Tumor-targeting monoclonal antibodies are available for a number of cancer cell types (over)expressing the corresponding tumor antigens. Such antibodies can limit tumor progression by different mechanisms, including direct growth inhibition and immune-mediated mechanisms, in particular complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and antibody-dependent cellular cytotoxicity (ADCC). ADCC can be mediated by various types of immune cells, including neutrophils, the most abundant leukocyte in circulation. Neutrophils express a number of Fc receptors, including Fcγ- and Fcα-receptors, and can therefore kill tumor cells opsonized with either IgG or IgA antibodies. In recent years, important insights have been obtained with respect to the mechanism(s) by which neutrophils engage and kill antibody-opsonized cancer cells and these findings are reviewed here. In addition, we consider a number of additional ways in which neutrophils may affect cancer progression, in particular by regulating adaptive anti-cancer immunity.
Topics: Humans; Neutrophils; Antibody-Dependent Cell Cytotoxicity; Receptors, Fc; Neoplasms; Antibodies, Monoclonal; Receptors, IgG
PubMed: 36331258
DOI: 10.1111/imr.13159 -
Blood May 2020
Topics: Animals; Erythrocyte Transfusion; Erythrocytes; Glycoproteins; Inflammation; Mice; Poly I-C
PubMed: 32463889
DOI: 10.1182/blood.2020005971 -
Journal of Nanobiotechnology Oct 2023Nanoparticles represent one of the most important innovations in the medical field. Among nanocarriers, polymeric nanoparticles (PNPs) attracted much attention due to...
BACKGROUND
Nanoparticles represent one of the most important innovations in the medical field. Among nanocarriers, polymeric nanoparticles (PNPs) attracted much attention due to their biodegradability, biocompatibility, and capacity to increase efficacy and safety of encapsulated drugs. Another important improvement in the use of nanoparticles as delivery systems is the conjugation of a targeting agent that enables the nanoparticles to accumulate in a specific tissue. Despite these advantages, the clinical translation of therapeutic approaches based on nanoparticles is prevented by their interactions with blood proteins. In fact, the so-formed protein corona (PC) drastically alters the biological identity of the particles. Adsorbed activated proteins of the complement cascade play a pivotal role in the clearance of nanoparticles, making them more easily recognized by macrophages, leading to their rapid elimination from the bloodstream and limiting their efficacy. Since the mouse is the most used preclinical model for human disease, this work compared human and mouse PC formed on untargeted PNPs (uPNPs) and targeted PNPs (tPNPs), paying particular attention to complement activation.
RESULTS
Mouse and human serum proteins adsorbed differently to PNPs. The differences in the binding of mouse complement proteins are minimal, whereas human complement components strongly distinguish the two particles. This is probably due to the human origin of the Fc portion of the antibody used as targeting agent on tPNPs. tPNPs and uPNPs mainly activate complement via the classical and alternative pathways, respectively, but this pattern did not affect their binding and internalization in macrophages and only a limited consumption of the activity of the human complement system was documented.
CONCLUSIONS
The results clearly indicate the presence of complement proteins on PNPs surface but partially derived from an unspecific deposition rather than an effective complement activation. The presence of a targeting antibody favors the activation of the classical pathway, but its absence allows an increased activation of the alternative pathway. This results in similar opsonization of both PNPs and similar phagocytosis by macrophages, without an impairment of the activity of circulating complement system and, consequently, not enhancing the susceptibility to infection.
Topics: Humans; Mice; Animals; Protein Corona; Opsonization; Complement System Proteins; Antibodies; Polymers; Nanoparticles
PubMed: 37838659
DOI: 10.1186/s12951-023-02134-4 -
Immunological Reviews Nov 2016Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The... (Review)
Review
Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The complement system, a crucial part of innate immunity, plays an important role in this process. Thus, apoptotic and necrotic cells are recognized by complement initiators such as C1q, mannose binding lectin, ficolins, and properdin. This triggers complement activation and opsonization of cells with fragments of C3b, which enhances phagocytosis and thus ensures silent removal. Importantly, the process is tightly controlled by the binding of complement inhibitors C4b-binding protein and factor H, which attenuates late steps of complement activation and inflammation. Furthermore, factor H becomes actively internalized by apoptotic cells, where it catalyzes the cleavage of intracellular C3 to C3b. The intracellularly derived C3b additionally opsonizes the cell surface further supporting safe and fast clearance and thereby aids to prevent autoimmunity. Internalized factor H also binds nucleosomes and directs monocytes into production of anti-inflammatory cytokines upon phagocytosis of such complexes. Disturbances in the complement-mediated clearance of dying cells result in persistence of autoantigens and development of autoimmune diseases like systemic lupus erythematosus, and may also be involved in development of age-related macula degeneration.
Topics: Animals; Apoptosis; Complement Activation; Complement Factor H; Complement System Proteins; Humans; Immunity, Innate; Inflammation; Lupus Erythematosus, Systemic; Monocytes; Necrosis; Phagocytosis
PubMed: 27782329
DOI: 10.1111/imr.12462 -
Infection and Drug Resistance 2019Removal of the spleen had already been established as a routine technique to treat splenic trauma and other diseases affecting the spleen before the anatomy, physiology,... (Review)
Review
Removal of the spleen had already been established as a routine technique to treat splenic trauma and other diseases affecting the spleen before the anatomy, physiology, and function of the spleen were known in the mid-twentieth century. It is now widely accepted that the splenectomized individual is at increased risk for infection, in particular, overwhelming post-splenectomy infection (OPSI). OPSI is a syndrome of fulminant sepsis occurring in splenectomized (asplenic) or hyposplenic individuals that is associated with high mortality and morbidity. Poorly opsonized bacteria such as encapsulated bacteria, in particular, , are often implicated in sepsis. The spleen is a reticuloendothelial organ that facilitates opsonization and phagocytosis of pathogens, in addition to cellular maintenance. Splenectomy is associated with an impairment in immunoglobulin production, antibody-mediated clearance, and phagocytosis, leading to an increased risk of infection and sepsis. Early identification of the at-risk patient, early blood cultures prior to antibiotic administration, urgent blood smears and fast pathogen-detection tests, and sepsis bundles should be utilized in these patients. Prompt management and aggressive treatment can alter the course of disease in the at-risk splenectomized patient. Overwhelming post-splenectomy infection can be prevented through vaccination, chemoprophylaxis, and patient education. This article evaluates post-splenectomy sepsis by summarizing the anatomy and function of the spleen, physiological changes after splenectomy that predispose the splenectomized patient to infection, and current management and prevention strategies.
PubMed: 31571940
DOI: 10.2147/IDR.S179902 -
Methods in Molecular Biology (Clifton,... 2023Phagocytosis is relevant for many research fields and is often measured as a functional outcome. However, accurate quantification can be challenging, and many...
Phagocytosis is relevant for many research fields and is often measured as a functional outcome. However, accurate quantification can be challenging, and many researchers find it difficult to study in a robust manner. There are many ways to measure phagocytosis, but what is often overlooked is the importance of experimental design and how the analysis is planned and performed. Experimental factors like reaction volume, time, and phagocyte-prey concentrations often have a large impact on the outcome, as is the choice of detection strategy with different fluorescent or colorimetric labels of prey and phagocyte. By using dose-response curve principles for both experimental design and analysis, it is possible to increase the sensitivity and robustness, leading to accurate quantification of phagocytosis that is comparable across experiments and systems.Here, we describe how to quantify phagocytosis using flow cytometry with a robust, high-throughput, and easy-to-use approach. The prey is first fluorescently double stained, followed by optional opsonization before being introduced to the phagocyte in a wide range of ratios. After incubation, data is acquired through flow cytometry. It can be assessed on both the population and single-cell level of the phagocytes, separating adhesion and internalization. As an example, we provide an experimental protocol for studying phagocytosis of opsonized Streptococcus pyogenes using the THP-1 cell line. This approach is easily incorporated into most existing phagocytosis assays and allows for reproducible results with high sensitivity.
Topics: Flow Cytometry; Phagocytosis; Phagocytes; Coloring Agents; Streptococcus pyogenes
PubMed: 37258971
DOI: 10.1007/978-1-0716-3243-7_15 -
Shock (Augusta, Ga.) Nov 2020Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its... (Review)
Review
Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its clinical presentation can vary from the asymptomatic state to acute respiratory distress syndrome (ARDS) and multi-organ dysfunction. Due to our insufficient understanding of its pathophysiology and lack of effective treatment, the morbidity and mortality of severe COVID-19 patients are high. Patients with COVID-19 develop ARDS fueled by exaggerated neutrophil influx into the lungs and cytokine storm. B-1a cells represent a unique subpopulation of B lymphocytes critical for circulating natural antibodies, innate immunity, and immunoregulation. These cells spontaneously produce natural IgM, interleukin (IL)-10, and granulocyte-monocyte colony stimulating factor (GM-CSF). Natural IgM neutralizes viruses and opsonizes bacteria, IL-10 attenuates the cytokine storm, and GM-CSF induces IgM production by B-1a cells in an autocrine manner. Indeed, B-1a cells have been shown to ameliorate influenza virus infection, sepsis, and pneumonia, all of which are similar to COVID-19. The recent discovery of B-1a cells in humans further reinforces their potentially critical role in the immune response against SARS-CoV-2 and their anticipated translational applications against viral and microbial infections. Given that B-1a cells protect against ARDS via immunoglobulin production and the anti-COVID-19 effects of convalescent plasma treatment, we recommend that studies be conducted to further examine the role of B-1a cells in the pathogenesis of COVID-19 and explore their therapeutic potential to treat COVID-19 patients.
Topics: Adoptive Transfer; Animals; B-Lymphocyte Subsets; Betacoronavirus; COVID-19; Coronavirus Infections; Host-Pathogen Interactions; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32604223
DOI: 10.1097/SHK.0000000000001610 -
Journal of Controlled Release :... Oct 2021The complement system plays a key role in opsonization and immune clearance of engineered nanoparticles. Understanding the efficiency, inter-subject, and inter-strain...
The complement system plays a key role in opsonization and immune clearance of engineered nanoparticles. Understanding the efficiency, inter-subject, and inter-strain differences of complement opsonization in preclinical species can help with translational nanomedicine development and improve our ability to model complement response in humans. Dextran-coated superparamagnetic iron oxide (SPIO) nanoparticles and a wide range of non-magnetic iron oxide nanoparticle formulations are widely used in magnetic resonance imaging and as clinically approved iron supplements. Previously we found that opsonization of SPIO nanoworms (NW) with the third complement protein (C3) proceeds mostly via the alternative pathway in humans, and via the lectin pathway in mice. Here, we studied the pathway and efficiency of opsonization of 106 nm SPIO NW with C3 in different preclinical species and commonly used laboratory strains. In sera of healthy human donors (n = 6), C3 opsonization proceeded exclusively through the alternative pathway. On the other hand, the C3 opsonization in dogs (6 breeds), rats (4 strains) and mice (5 strains) sera was either partially or completely dependent on the complement Ca-sensitive pathways (lectin and/or classical). Specifically, C3 opsonization in sera of Long Evans rat strain, and mouse strains widely used in nanomedicine research (BALB/c, C57BL/6 J, and A/J) was only through the Ca-dependent pathways. Dogs and humans had the highest between-subject variability in C3 opsonization levels, while rat and mouse sera showed the lowest between-strain variability. Furthermore, using a panel of SPIO nanoparticles of different sizes and dextran coatings, we found that the level of C3 opsonization (C3 molecules per milligram Fe) in human sera was lower than in animal sera. At the same time, there was a strong predictive value of complement opsonization in dog and rat sera; nanoparticles with higher C3 deposition in animals showed higher deposition in humans, and vice versa. Notably, the opsonization decreased with decreasing size in all sera. The studies highlight the importance of the consideration of species and strains for predicting human complement responses (opsonization) towards nanomedicines.
Topics: Animals; Complement Activation; Complement C3; Dogs; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Rats; Rats, Long-Evans
PubMed: 34481928
DOI: 10.1016/j.jconrel.2021.08.048