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Journal of Neuroimmune Pharmacology :... Sep 2020Extracellular signaling is pivotal to maintain organismal homeostasis. A quickly emerging field of interest within extracellular signaling is the study of extracellular... (Review)
Review
Extracellular signaling is pivotal to maintain organismal homeostasis. A quickly emerging field of interest within extracellular signaling is the study of extracellular vesicles (EV), which act as messaging vehicles for nucleic acids, proteins, metabolites, lipids, etc. from donor cells to recipient cells. This transfer of biologically active material within a vesicular body is similar to the infection of a cell through a virus particle, which transfers genetic material from one cell to another to preserve an infection state, and viruses are known to modulate EV. Although considerable heterogeneity exists within EV and viruses, this review focuses on those that are small (< 200 nm in diameter) and of relatively low density (< 1.3 g/mL). A multitude of isolation methods for EV and virus particles exist. In this review, we present an update on methods for their isolation, purification, and phenotypic characterization. We hope that the information we provide will be of use to basic science and clinical investigators, as well as biotechnologists in this emerging field. Graphical Abstract.
Topics: Animals; Cell Communication; Exosomes; Extracellular Space; Extracellular Vesicles; Humans; Nanoparticles; Viruses
PubMed: 31512168
DOI: 10.1007/s11481-019-09874-x -
Allergology International : Official... Jan 2021Neutrophils and eosinophils are granulocytes which are characterized by the presence of granules in the cytoplasm. Granules provide a safe storage site for granule... (Review)
Review
Neutrophils and eosinophils are granulocytes which are characterized by the presence of granules in the cytoplasm. Granules provide a safe storage site for granule proteins that play important roles in the immune function of granulocytes. Upon granulocytes activation, diverse proteins are released from the granules into the extracellular space and contribute to the fight against infections. In this article, we describe granule proteins of both neutrophils and eosinophils able to kill pathogens and review their anticipated mechanism of antimicrobial toxicity. It should be noted that an excess of granules protein release can lead to tissue damage of the host resulting in chronic inflammation and organ dysfunction.
Topics: Cell Communication; Cytotoxicity, Immunologic; Disease Susceptibility; Eosinophil Granule Proteins; Eosinophils; Extracellular Space; Host-Pathogen Interactions; Humans; Immunity, Innate; Neutrophils
PubMed: 33277190
DOI: 10.1016/j.alit.2020.11.003 -
Cell Stress & Chaperones May 2018Small heat shock proteins (sHsps) belong to the family of heat shock proteins (Hsps): some are induced in response to multiple stressful events to protect the cells... (Review)
Review
Small heat shock proteins (sHsps) belong to the family of heat shock proteins (Hsps): some are induced in response to multiple stressful events to protect the cells while others are constitutively expressed. Until now, it was believed that Hsps, including sHsps, are present inside the cells and perform intracellular functions. Interestingly, several groups recently reported the extracellular presence of Hsps, and sHsps have also been detected in sera/cerebrospinal fluids in various pathological conditions. Secretion into the extracellular milieu during many pathological conditions suggests additional or novel functions of sHsps in addition to their intracellular properties. Extracellular sHsps are implicated in cell-cell communication, activation of immune cells, and promoting anti-inflammatory and anti-platelet responses. Interestingly, exogenous administration of sHsps showed therapeutic effects in multiple disease models implying that extracellular sHsps are beneficial in pathological conditions. sHsps do not possess signal sequence and, hence, are not exported through the classical Endoplasmic reticulum-Golgi complex (ER-Golgi) secretory pathway. Further, export of sHsps is not inhibited by ER-Golgi secretory pathway inhibitors implying the involvement of a nonclassical secretory pathway in sHsp export. In lieu, lysoendosomal and exosomal pathways have been proposed for the export of sHsps. Heat shock protein 27 (Hsp27), αB-crystallin (αBC), and Hsp20 are shown to be exported by exosomes. Exosomes packaged with sHsps have beneficial effects in in vivo disease models. However, secretion mechanisms and therapeutic use of sHsps have not been elucidated in detail. Therefore, this review aimed at highlighting the current understanding of sHsps (Hsp27, αBC, and Hsp20) in the extracellular medium.
Topics: Animals; Exosomes; Extracellular Space; Heat-Shock Proteins, Small; Humans; Models, Biological
PubMed: 29086335
DOI: 10.1007/s12192-017-0856-z -
Journal of Computational Neuroscience Dec 2010
Topics: Animals; Brain; Congresses as Topic; Electrophysiological Phenomena; Evoked Potentials; Extracellular Space; Humans; Models, Neurological
PubMed: 20936339
DOI: 10.1007/s10827-010-0283-y -
International Journal of Molecular... Nov 2022Here, we link approved and emerging nucleic acid-based therapies with the expanding universe of small non-coding RNAs (sncRNAs) and the innate immune responses that... (Review)
Review
Here, we link approved and emerging nucleic acid-based therapies with the expanding universe of small non-coding RNAs (sncRNAs) and the innate immune responses that sense oligonucleotides taken up into endosomes. The Toll-like receptors (TLRs) 3, 7, 8, and 9 are located in endosomes and can detect nucleic acids taken up through endocytic routes. These receptors are key triggers in the defense against viruses and/or bacterial infections, yet they also constitute an Achilles heel towards the discrimination between self- and pathogenic nucleic acids. The compartmentalization of nucleic acids and the activity of nucleases are key components in avoiding autoimmune reactions against nucleic acids, but we still lack knowledge on the plethora of nucleic acids that might be released into the extracellular space upon infections, inflammation, and other stress responses involving increased cell death. We review recent findings that a set of single-stranded oligonucleotides (length of 25-40 nucleotides (nt)) can temporarily block ligands destined for endosomes expressing TLRs in human monocyte-derived dendritic cells. We discuss knowledge gaps and highlight the existence of a pool of RNA with an approximate length of 30-40 nt that may still have unappreciated regulatory functions in physiology and in the defense against viruses as gatekeepers of endosomal uptake through certain routes.
Topics: Humans; Antiviral Agents; Oligonucleotides; Extracellular Space; Toll-Like Receptors; Immunity, Innate; Viruses; Nucleic Acids
PubMed: 36498932
DOI: 10.3390/ijms232314593 -
Progress in Neurobiology Oct 2017Although neurons attract the most attention in neurobiology, our current knowledge of neural circuit can only partially explain the neurological and psychiatric... (Review)
Review
Although neurons attract the most attention in neurobiology, our current knowledge of neural circuit can only partially explain the neurological and psychiatric conditions of the brain. Thus, it is also important to consider the influence of brain interstitial system (ISS), which refers to the space among neural cells and capillaries. The ISS is the major compartment of the brain microenvironment that provides the immediate accommodation space for neural cells, and it occupies 15% to 20% of the total brain volume. The brain ISS is a dynamic and complex space connecting the vascular system and neural networks and it plays crucial roles in substance transport and signal transmission among neurons. Investigation of the brain ISS can provide new perspectives for understanding brain architecture and function and for exploring new strategies to treat brain disorders. This review discussed the anatomy of the brain ISS under both physiological and pathological conditions, biophysical modeling of the brain ISS and in vivo measurement and imaging techniques, including recent findings on brain ISS divisions. Moreover, the implications of ISS knowledge for basic neuroscience and clinical applications are addressed.
Topics: Animals; Brain; Extracellular Space; Humans
PubMed: 26837044
DOI: 10.1016/j.pneurobio.2015.12.007 -
American Journal of Physiology.... Aug 2020Complex organisms rely heavily on intercellular communication. The rapidly expanding field of extracellular vesicle biology has made it clear that the necessary... (Review)
Review
Complex organisms rely heavily on intercellular communication. The rapidly expanding field of extracellular vesicle biology has made it clear that the necessary intercellular communication occurs partly through their paracrine and endocrine actions. Extracellular vesicles are nanoscale lipid membranes (30-2,000 nm in diameter) that shuttle functional biological material between cells. They are released from numerous tissues and are isolated from nearly all biofluids and cell cultures. Although their biogenesis, cell targeting, and functional roles are incompletely understood, they appear to have crucial roles in physiological and disease processes. Their enormous potential to serve as sensitive biomarkers of disease and also new therapeutic interventions for diseases have gained them considerable attention in recent years. Regular physical exercise training confers systemic health benefits and consequently prevents many age-related degenerative diseases. Many of the molecular mechanisms responsible for the salubrious effects of exercise are known, yet a common underlying mechanism potentially responsible for the holistic health benefits of exercise has only recently been explored (i.e., via extracellular vesicle transport of biological material). Here, we provide an overview of extracellular vesicle biology before outlining the current evidence on the capacity for a single bout and chronic exercise to elicit changes in extracellular vesicle content and modulate their molecular cargo (e.g., small RNAs). We highlight areas for future research and emphasize their potential utility as biomarkers and therapeutic strategies of disease and its prevention.
Topics: Animals; Cell Communication; Exercise; Extracellular Space; Extracellular Vesicles; Health Promotion; Heart Diseases; Humans; MicroRNAs; Physical Conditioning, Animal; Primary Prevention
PubMed: 32603601
DOI: 10.1152/ajpendo.00215.2020 -
Frontiers in Immunology 2019Interleukin 26 (IL-26) is the most recently identified member of the IL-20 cytokine subfamily, and is a novel mediator of inflammation overexpressed in activated or... (Review)
Review
Interleukin 26 (IL-26) is the most recently identified member of the IL-20 cytokine subfamily, and is a novel mediator of inflammation overexpressed in activated or transformed T cells. Novel properties have recently been assigned to IL-26, owing to its non-conventional cationic, and amphipathic features. IL-26 binds to DNA released from damaged cells and, as a carrier molecule for extracellular DNA, links DNA to inflammation. This observation suggests that IL-26 may act both as a driver and an effector of inflammation, leading to the establishment of a deleterious amplification loop and, ultimately, sustained inflammation. Thus, IL-26 emerges as an important mediator in local immunity/inflammation. The dysregulated expression and extracellular DNA carrier capacity of IL-26 may have profound consequences for the chronicity of inflammation. IL-26 also exhibits direct antimicrobial properties. This review summarizes recent advances on the biology of IL-26 and discusses its roles as a novel kinocidin.
Topics: Animals; Cytokines; Disease Susceptibility; Extracellular Space; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Inflammation; Inflammation Mediators; Interleukins; Signal Transduction; Structure-Activity Relationship
PubMed: 30809226
DOI: 10.3389/fimmu.2019.00204 -
Methods in Molecular Biology (Clifton,... 2018Extracellular RNA (exRNA) has recently expanded as a highly important area of study in biomarker discovery and cancer therapeutics. exRNA consists of diverse RNA... (Review)
Review
Extracellular RNA (exRNA) has recently expanded as a highly important area of study in biomarker discovery and cancer therapeutics. exRNA consists of diverse RNA subpopulations that are normally protected from degradation by incorporation into membranous vesicles or by lipid/protein association. They are found circulating in biofluids, and have proven highly promising for minimally invasive diagnostic and prognostic purposes, particularly in oncology. Recent work has made progress in our understanding of exRNAs-from their biogenesis, compartmentalization, and vesicle packaging to their various applications as biomarkers and therapeutics, as well as the new challenges that arise in isolation and purification for accurate and reproducible analysis. Here we review the most recent advancements in exRNA research.
Topics: Animals; Extracellular Space; Extracellular Vesicles; Humans; MicroRNAs; RNA; RNA, Messenger
PubMed: 29388131
DOI: 10.1007/978-1-4939-7652-2_1 -
Developmental Cell Jul 2011Extracellular signaling molecules have crucial roles in development and homeostasis, and their incorrect deployment can lead to developmental defects and disease states.... (Review)
Review
Extracellular signaling molecules have crucial roles in development and homeostasis, and their incorrect deployment can lead to developmental defects and disease states. Signaling molecules are released from sending cells, travel to target cells, and act over length scales of several orders of magnitude, from morphogen-mediated patterning of small developmental fields to hormonal signaling throughout the organism. We discuss how signals are modified and assembled for transport, which routes they take to reach their targets, and how their range is affected by mobility and stability.
Topics: Animals; Biological Transport; Cells; Endocytosis; Extracellular Matrix; Extracellular Space; Humans; Movement; Signal Transduction
PubMed: 21763615
DOI: 10.1016/j.devcel.2011.06.001