NETosis: Immunity, Pathogenesis and Therapeutics takes a focused approach to the clinical aspects of NETosis and drug development, bringing critical findings. Chapters introduce NETosis, consider mechanisms and antimicrobial strategies regulating NETosis, examine NETosis in neonates, explore the role of NETosis in autoimmunity, delve into NETosis and other diseases, and present therapeutic approaches for dysregulated NETosis. Since Brinkamm, et al, discovered an unrecognized neutrophil anti-microbial mechanism responsible for the extracellular killing of invading pathogens in 2004, the novel process in which nuclear chromatin de-condenses and DNA is ejected into the extra cellular environment, trapping and inactivating tissue pathogens has rapidly evolved. Presents an up-to-date and detailed analysis of NETosis Brings together critical findings on NETosis as a comparatively novel immune mechanism Focuses on the clinical aspects of NETosis that lead to drug development Covers the topic with a cogency and passion that is based on years of scientific research
NETosis, a form of cell death that manifests by the release of decondensed chromatin to the extracellular space, provides valuable insights into mechanisms and consequences of cellular demise. Because extracellular chromatin can immobilize microbes, the extended nucleohistone network was called a neutrophil extracellular trap (NET), and the process of chromatin release was proposed to serve an innate immune defense function. Extracellular chromatin NETs were initially observed in studies of neutrophils and are most prominent in these types of granulocytes. Subsequent studies showed that other granulocytes and, in a limited way, other cells of the innate immune response may also release nuclear chromatin following certain kinds of stimulation. Variations of NETosis were noted with cells that remain temporarily motile after the release of chromatin. Numerous stimuli for NETosis were discovered, including bacterial breakdown products, inflammatory stimuli, particulate matter, certain crystals, immune complexes and activated thrombocytes. Fundamental explorations into the mechanisms of NETosis observed that neutrophil enzyme activity (PAD4, neutrophil elastase, proteinase 3 and myeloperoxidase) and signal transduction pathways contribute to the regulation of NETosis. Histones in NET chromatin become modified by peptidylarginine deiminase 4 (PAD4) and cleaved at specific sites by proteases, leading to extensive chromatin externalization. In addition, NETs serve for attachment of bactericidal enzymes including myeloperoxidase, leukocyte proteases, and the cathelicidin LL-37. NETs are decorated with proteases and may thus contribute to tissue destruction. However, the attachment of these enzymes to NET-associated supramolecular structures restricts systemic spread of the proteolytic activity. While the benefit of NETs in an infection appears obvious, NETs also participate as key protagonists in various pathologic states. Therefore, it is essential for NETs to be efficiently cleared; otherwise digestive enzymes may gain access to tissues where inflammation takes place. Persistent NET exposure at sites of inflammation may lead to a further complication: NET antigens may provoke acquired immune responses and, over time, could initiate autoimmune reactions, serve as antigen for nuclear autoantibodies and foster DNA immune complex-related inflammation. Neutrophil products and deiminated proteins comprise an important group of autoantigens in musculoskeletal disorders. Aberrant NET synthesis and/or clearance are often associated with inflammatory and autoimmune conditions. Recent evidence also implicates aberrant NET formation in the development of endothelial damage, atherosclerosis and thrombosis. Intravital microscopy provides evidence for conditions that induce NETosis in vivo. Furthermore, NETs can easily be detected in synovial fluid and tissue sections of patients with arthritis and gout. NETosis is thus of interest to researchers who investigate innate immune responses, host-pathogen interactions, chronic inflammatory disorders, cell and vascular biology, biochemistry, and autoimmunity. As we enter the second decade of research on NETosis, it is useful and timely to review the mechanisms and pathways of NET formation, their role in bacterial and fungal defense and their importance as inducers of autoimmune responses.
|Author||: Mariana J. Kaplan,Marko Radic|
|Publisher||: Frontiers E-books|
|Release Date||: 2013-08-08|
|ISBN 10||: 2889191583|
|Pages||: 329 pages|
NETosis is a unique form of cell death that is characterized by the release of decondensed chromatin and granular contents to the extracellular space. The initial observation of NETosis placed the process within the context of the innate immune response to infections. Neutrophils, the most numerous leukocytes that arrive quickly at the site of an infection, were the first cell type shown to undergo extracellular trap formation. However, subsequent studies showed that other granulocytes are also capable of releasing nuclear chromatin following stimulation. The extracellular chromatin acts to immobilize microbes and prevent their dispersal in the host. Bacterial breakdown products and inflammatory stimuli induce NETosis and the release of NETs requires enzyme activities. Histones in NET chromatin become modified by peptidylarginine deiminase 4 (PAD4) and cleaved at specific sites by proteases. NETs serve for attachment of bactericidal enzymes including myeloperoxidase, leukocyte proteases, and the cathelicidin LL-37. While the benefit of NETs in an infection appears clear, NETs also figure prominently at the center of various pathologic states. Therefore, it is important for NETs to be efficiently cleared; else digestive enzymes may gain access to tissues where inflammation takes place. Persistent NET exposure at sites of inflammation may lead to a further complication: NET antigens may provoke acquired immune responses and, over time, could initiate autoimmune reactions. Recent studies identified aberrant NET synthesis and/or clearance in inflammatory/autoimmune conditions such as systemic lupus erythematosus (SLE), psoriasis, ANCA-positive vasculitis, gout and Felty’s syndrome. In the case of SLE, for example, it appears that LL-37 exposed in the NETs may be a significant trigger of type I Interferon responses in this disease. Recent evidence also implicates aberrant NET formation in the development of endothelial damage, atherosclerosis and thrombosis. NETosis is thus of interest to researchers who investigate innate immune responses, host-pathogen interactions, chronic inflammatory disorders, cell and vascular biology, biochemistry, and autoimmunity. As we approach the 10-year-anniversary of the initial discovery of NETosis, it is useful and timely to review the so far identified mechanisms and pathways of NET formation, their role in bacterial and fungal defense and their putative importance as inducers of autoimmune responses. We look forward to a rich and rigorous discussion of these and related issues that benefit from interdisciplinary approaches, collaborations and exciting discoveries.
Inflammation is important in many diseases, yet it is hard to find current information on the pertinent cellular and molecular mechanisms of inflammation. This book is a current and authoritative review of various aspects of inflammation in mammalian organisms. Basic principles, including regulation by cytokines, lipid mediators, reactive oxygen species and leukocyte recruitment are followed by chapters on integrative aspects of inflammation, such as neutrophil extracellular traps, sepsis and granulomatous inflammation. Contents: TNF Superfamily in Inflammation (Marisol Veny, Richard Virgen-Slane and Carl F Ware) Complement as a Mediator of Inflammation (B Paul Morgan) Lipids and Inflammation (Valerie B O'Donnell, Robert C Murphy and Garret A FitzGerald) Reactive Oxygen Species (Ulla G Knaus) Leukocyte Adhesion (Klaus Ley and Zhichao Fan) Neutrophil Extracellular Traps (Tobias A Fuchs, Abdul Hakkim and Constantin F Urban) Sepsis (Jamison J Grailer, Matthew J Delano and Peter A Ward) Granulomatous Inflammation (Marc Hilhorst, Gene Hunder, Jörg Goronzy and Cornelia Weyand) Readership: Graduate students, medical doctors/ practitioners, researchers, pathologists and nutritionists in medicine and healthcare. Keywords: Cytokines;IL-1;TNF;Lipid Mediators;Bradykinin and Neuropeptides;Leukocyte Adhesion;Angiogenesis;Degranulation;Antimicrobial Peptides;Neutrophil Extracellular Traps (NETs);Pharmacologic Modulation of Inflammation;Sepsis;Complement;Oxygen Radicals;Reperfusion Injury;Resolution of Inflammation;Atherosclerosis;Granulomatous Inflammation;Inflammatory Bowel DiseaseReview: Key Features: Up-to-date resource Comprehensive review of the various facets of inflammation
This book highlights the important role of neutrophils in health as well as in the pathogenesis of various diseases. Section 1 provides a general background information regarding the mechanisms and various triggers of neutrophil extracellular traps (NETs) formation and their role in various infectious and noninfectious diseases (such as postinjury inflammation). Section 2 provides recent evidence regarding the role of neutrophils in the pathogenesis as well as a therapeutic target for selected disease conditions such as periodontal diseases, rheumatoid arthritis, and cystic fibrosis. Section 3 describes the anti-inflammatory properties of neutrophils with focus regarding their role in graft versus host disease. This book provides a wider picture with regard to the importance of this immune cell type in various diseases with focus on one of its recently discovered properties, NETs. Therapeutic targets aimed to modulate neutrophil functions might provide novel approaches in the treatment of various diseases of infectious and noninfectious origin.
|Author||: Hector Enrique Munoz|
|Release Date||: 2020|
|Pages||: 176 pages|
The cell mechanical phenotype is a useful measure to understand cell identity and state. Cell mechanical properties such as deformability can provide an understanding of cellular processes or intracellular composition without direct labeling. The cell nucleus is a significant component of the cell and it is useful to understand how it impacts cell deformability. However, high throughput methods to measure cell deformability largely cannot directly integrate nuclear information. Here we present fluorescent imaging deformability cytometry (FI-DC), a high throughput platform capable of measuring cells in flow at 0.5 m/s, while providing simultaneous brightfield and fluorescent images. This technology enables us to identify cell subpopulations by their nuclear structure, as well as identify neutrophils undergoing neutrophil extracellular trap (NET) generation.
|Author||: Mohd Hilmi Abu Bakar|
|Publisher||: GRIN Verlag|
|Release Date||: 2019-08-08|
|ISBN 10||: 3668995664|
|Pages||: 27 pages|
Abstract from the year 2019 in the subject Medicine - Public Health, grade: 10.0, , language: English, abstract: This work is a collection of studies concerning human sustainability. We were proud for having Postgrad Colloquium 2019, Faculty of Health Sciences Universiti Sultan Zainal Abidin (UniSZA). It was held on 30th April 2019 at Academic Building UniSZA Main Campus Kuala Nerus, Terengganu, Malaysia. Total of 24 students including 15 students from Laboratory Based Research category and 9 students from Community Based Research category of Faculty Health Sciences and Faculty of Medicine were participated. We congratulated to the winners Omar Mahmoud Said Alshajrawi from Faculty of Medicine, Masters student for the Laboratory Based Research category and Mohd Ibrahim Abdullah from Faculty of Health Sciences, Doctorate student for the Community Based Research category. Both of you were pretty amazing. See again next year on 2020 to all researchers.
This book, an international collaborative effort in the area of molecular respiratory research, showcases a broad range of multidisciplinary approaches to unravel and analyze the underlying mechanisms of a spectrum of respiratory ailments. It discusses immunological and genetic respiratory disorders, cancer, respiratory allergies and cough, sleep disordered breathing and many others. Exciting new results and up-to-date critical overviews of widely debated topics pertaining to respiratory disorders are presented. The contributions provide evidence for the growing interest of the international community of researchers in the field of respiration. The book incorporates modern molecular approaches to diagnostic and treatment solutions, underscoring the need for rational, evidence-based treatment methods. Combining cutting edge basic and clinical research with expert knowledge and experience this book is essential reading for medical students, research scientists and practicing specialists in pulmonology, immunology and allergology.
|Release Date||: 2017|
|Pages||: 39 pages|
|Release Date||: 2020|
|ISBN 10||: 9789176199817|
|Pages||: 329 pages|
These volumes teach readers to think beyond apoptosis and describes all of the known processes that cells can undergo which result in cell death This two-volume source on how cells dies is the first, comprehensive collection to cover all of the known processes that cells undergo when they die. It is also the only one of its kind to compare these processes. It seeks to enlighten those in the field about these many processes and to stimulate their thinking at looking at these pathways when their research system does not show signs of activation of the classic apoptotic pathway. In addition, it links activities like the molecular biology of one process (eg. Necrosis) to another process (eg. apoptosis) and contrasts those that are close to each. Volume 1 of Apoptosis and Beyond: The Many Ways Cells Die begins with a general view of the cytoplasmic and nuclear features of apoptosis. It then goes on to offer chapters on targeting the cell death mechanism; microbial programmed cell death; autophagy; cell injury, adaptation, and necrosis; necroptosis; ferroptosis; anoikis; pyronecrosis; and more. Volume 2 covers such subjects as phenoptosis; pyroptosis; hematopoiesis and eryptosis; cyclophilin d-dependent necrosis; and the role of phospholipase in cell death. Covers all known processes that dying cells undergo Provides extensive coverage of a topic not fully covered before Offers chapters written by top researchers in the field Provides activities that link and contrast processes to each other Apoptosis and Beyond: The Many Ways Cells Die will appeal to students and researchers/clinicians in cell biology, molecular biology, oncology, and tumor biology.
The definitive survey of diagnostic dermatopathology—and the single-best resource for addressing differential diagnosis at the microscopic level For virtually every kind of skin lesion, this skill-sharpening resource has everything clinicians need to successfully perform differential diagnosis at the microscopic level. Dermatopathology features a systematic, algorithmic approach that cuts through the complexity of the discipline’s traditional disease-oriented focus, providing a ready-to-use diagnostic tool that puts the entire world of dermatopathology into perspective. This classic has won acclaim as the only dermatology pathology resource that is valuable for both teaching and for clinical practice and differential diagnosis. While other references may be more exhaustive, denser, or larger, none are more clinically useful as Dermatopathology. With 25% of the dermatology board and recertification examination consisting of dermatopathology topics, this is also an outstanding board review tool. Filled with hundreds of color photomicrographs, the book features a clear five-part organization and nearly forty detailed chapters—each reflecting the scientifically rigorous, up-to-date insights of authors who are acknowledged experts in the field. The book’s vast scope encompasses all skin disease processes—inflammatory, non-inflammatory, infections, and proliferations (harmatomas, hyperplasias, and neoplasms, plus disorders of nails and oral mucosa). •Includes Online Image Bank containing all the images in the book•Increased number of full-color images•Numerous tables assist clinicians differentiate similar conditions from one another•NEW CHAPTERS on laboratory methods and stains, and updated immunohistochemistry content
Publisher's Note: Products purchased from Third Party sellers are not guaranteed by the publisher for quality, authenticity, or access to any online entitlements included with the product. The world's most highly regarded reference text on the mechanisms and clinical management of blood diseases A Doody's Core Title for 2019! Edition after edition, Williams Hematology has guided generations of clinicians, biomedical researchers, and trainees in many disciplines through the origins, pathophysiological mechanisms, and management of benign and malignant disorders of blood cells and coagulation proteins. It is acknowledged worldwide as the leading hematology resource, with editors who are internationally regarded for their research and clinical achievements and authors who are luminaries in their fields. The Ninth Edition of Williams Hematology is extensively revised to reflect the latest advancements in basic science, translational pathophysiology, and clinical practice. In addition to completely new chapters, it features a full-color presentation that includes 700 photographs, 300 of which are new to this edition, and 475 illustrations. Recognizing that blood and marrow cell morphology is at the heart of diagnostic hematology, informative color images of the relevant disease topics are conveniently integrated into each chapter, allowing easy access to illustrations of cell morphology important to diagnosis. Comprehensive in its depth and breath, this go-to textbook begins with the evaluation of the patient and progresses to the molecular and cellular underpinnings of normal and pathological hematology. Subsequent sections present disorders of the erythrocyte, granulocytes and monocytes, lymphocytes and plasma cells, malignant myeloid and lymphoid diseases, hemostasis and thrombosis, and transfusion medicine.
A unique case-based molecular approach to understanding pathology Pathology: A Modern Case Study is a concise, focused text that emphasizes the molecular and cellular biology essential to understanding the concepts of disease causation. The book includes numerous case studies designed to highlight the role of the pathologist in the team that provides patient care. Pathology: A Modern Case Study examines the role of anatomic, clinical, and molecular pathologists in dedicated chapters and in descriptions of the pathology of specific organ systems. Features Coverage of pathology focuses on modern approaches to common and important diseases Each chapter delivers the most up-to-date advances in pathology Learning aids include chapter summaries and overviews, bolded terms, and a glossary Common clinically relevant disease are highlighted Disease discussion is based on organ compartment and etiology Coverage includes: Disease and the Genome: Genetic, Developmental and Neoplastic Disease Cell Injury, Death and Aging and the Body's Response Environmental Injury Clinical Practice: Anatomic Pathology Clinical Practice: Molecular Pathology Clinical Practice: Molecular Pathology Organ-specific pathology covering all major body systems Molecular pathology Essential for undergraduate medical students and clinicians who wish to expand their knowledge pathology, Pathology: A Modern Case Study delivers valuable coverage that is directly related to a patient’s condition and the clinical practice of pathology.
This book provides a concise set of protocols for assessing basic neutrophil functions, investigating specialized areas in neutrophil research, and completing step-by-step diagnostic assays of common neutrophil disorders. Each of the protocols is written by leading researchers in the field and includes hints for success, as well as guidance for troubleshooting. Scientists and clinicians will find this collection an invaluable aid.
This book familiarizes the reader with some recent trends in the theory and practice of thrombolysis. It covers the field of fibrinolysis from the standpoint of basic scientists and clinicians and delivers the state-of-the-art information on the biochemistry and pharmacology of fibrinolysis, as well as related novel methodological and diagnostic tools in the field. An introductory chapter summarizes the basic molecular mechanisms in fibrinolysis (plasminogen, its endogenous activators and their inhibitors, plasmin and its inhibitors). Recent developments in our understanding of fibrin formation are described in the context of its impact on fibrinolysis. The discussion of neutrophil extracellular traps in the modulation of fibrin assembly and the consequences regarding plasminogen activation and plasmin action addresses a novel aspect of fibrinolysis.
|Author||: Luis Enrique Muñoz,Christian Berens,Kirsten Lauber|
|Publisher||: Frontiers Media SA|
|Release Date||: 2015-08-17|
|ISBN 10||: 2889196011|
|Pages||: 329 pages|
In multicellular organisms, states with a high degree of tissue turnover like embryogenesis, development, and adult tissue homeostasis need an instantaneous, tightly regulated and immunologically silent clearance of these dying cells to ensure appropriate development of the embryo and adult tissue remodelling. The proper and swift clearance of apoptotic cells is essential to prevent cellular leakage of damage associated molecular patterns (DAMPs) which would lead to the stimulation of inflammatory cytokine responses. In addition to the clearance of apoptotic cells (efferocytosis), backup mechanisms are required to cope with DAMPs (HMGB-1, DNA, RNA, S100 molecules, ATP and adenosine) and other intracellular material (uric acid, intracellular proteins and their aggregates) released from cells, that were not properly cleared and have entered the stage of secondary necrosis. Furthermore, under certain pathologic conditions (e.g. gout, cancer, diabetes) non-apoptotic cell death may transiently occur (NETosis, necroptosis, pyroptosis) which generates material that also has to be cleared to avoid overloading tissues with non-functional cellular waste. Efficient efferocytosis is therefore indispensable for normal tissue turnover and homeostasis. The characterization of various signalling pathways that regulate this complex and evolutionary conserved process has shed light on new pathogenetic mechanisms of many diseases. Impaired clearance promotes initiation of autoimmunity as well as the perpetuation of chronic inflammation, but may also foster anti-tumor immunity under certain microenvironmental conditions. Immunological tolerance is continuously being challenged by the presence of post-apoptotic remnants in peripheral lymphoid tissues. Besides the autoimmune phenotype of chronic inflammatory rheumatoid disorders a plethora of pathologies have been associated with defects in genes involved in clearance, e.g. atherosclerosis, cancer, gout, diabetes, some forms of blindness, neuropathy, schizophrenia and Alzheimer’s disease. The main goal of this research topic is to collect contributions from various disciplines committed to studying pathogenetic mechanisms of the aforementioned disorders and dealing with alterations in the clearance of dying and dead cells, their remnants, and their constituents that leak out after membrane rupture. Integrating the combined collection of knowledge on efferocytosis and clearance of dead cells and their derived waste from different fields of research in physiology and pathophysiology could improve the molecular understanding of these increasingly prevalent diseases and may ultimately result in new therapeutic strategies.
A Top 25 CHOICE 2016 Title, and recipient of the CHOICE Outstanding Academic Title (OAT) Award. How much energy is released in ATP hydrolysis? How many mRNAs are in a cell? How genetically similar are two random people? What is faster, transcription or translation?Cell Biology by the Numbers explores these questions and dozens of others provid
Surveys the biotechnologically influenced advances in the understanding of systemic autoimmune disorders, highlighting recent research using cell biology and biochemistry, the cloning of immune cells, recombinant DNA, and molecular genetics. Among the topics are the role of complement in inflammatio