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NETosis

NETosis
Immunity, Pathogenesis and Therapeutics

by Geeta Rai

  • Publisher : Academic Press
  • Release : 2019-06-01
  • Pages : 200
  • ISBN : 0128163798
  • Language : En, Es, Fr & De
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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 2: The Excitement Continues

NETosis 2: The Excitement Continues

by Mariana J. Kaplan,Marko Radic,Martin Herrmann

  • Publisher : Frontiers Media SA
  • Release : 2017-12-28
  • Pages : 129
  • ISBN : 2889453790
  • Language : En, Es, Fr & De
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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.

NETosis: At the Intersection of Cell Biology, Microbiology, and Immunology

NETosis: At the Intersection of Cell Biology, Microbiology, and Immunology
A Book

by Mariana J. Kaplan,Marko Radic

  • Publisher : Frontiers E-books
  • Release : 2013-08-08
  • Pages : 129
  • ISBN : 2889191583
  • Language : En, Es, Fr & De
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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.

Canine Neutrophils and Platelets in Sepsis

Canine Neutrophils and Platelets in Sepsis
Platelet Activation and Neutrophil Extracellular Trap Formation in an Ex Vivo Sepsis Model

by Ronald H. L. Li

  • Publisher : Unknown Publisher
  • Release : 2018
  • Pages : 129
  • ISBN : 9780355967395
  • Language : En, Es, Fr & De
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Sepsis remains one of the leading causes of death due to critical illness in human and veterinary medicine. Neutrophils release neutrophil extracellular traps (NETs) composed of cell-free DNA (cfDNA) decorated with histones and antimicrobial proteins. Platelets function as a primary effector cell of hemostasis, serving as innate immune cells in mice and humans by recognizing pathogens and interacting with neutrophils to induce NET formation (NETosis). Although NETs have protective roles in the initial stages of sepsis, excessive NET formation can induce thrombosis and multiple organ failure, both of which are associated with poor outcome in sepsis. Pathogen-induced NETosis and platelet activation have been extensively studied in septic mouse models but their effects on dogs with sepsis remain largely unknown. In this dissertation, we sought to characterize in vitro NETosis induced by E.coli lipopolysaccharide (LPS) and ex vivo NETosis in clinically septic dogs. Because platelet activation in sepsis may play a key role in facilitating NETosis in dogs, we also sought to study platelet activation and the role of TLR4 in response to LPS. The central hypothesis of this dissertation was that canine neutrophils undergo NETosis in response to LPS or naturally occurring bacterial infection. Specifically, we hypothesized that LPS-induced canine NETosis requires histone H3 citrullination by the enzyme, peptidyl arginine deiminase (PAD). In addition, we hypothesized that canine platelets express functional TLR4 mediating platelet activation in response to LPS. To characterize in vitro LPS-induced NETosis, cfDNA was quantified by spectrophotometry and a novel technique of NET identification was established using immunofluorescence microscopic colocalization of cfDNA, citrullinated histone H3 (citH3) and myeloperoxidase. LPS stimulation in canine neutrophils resulted in NETosis and intracellular citH3 expression. The role of the enzyme, peptidylarginine deiminase (PAD), in NETosis was assessed by treating LPS-activated neutrophils with the PAD-inhibitor, Cl-amidine. Cl-amidine attenuated NETosis and expression of intracellular citH3 indicating that LPS-induced NETosis in dogs is dependent on histone H3 citrullination and PAD. Ex vivo NETosis in septic foci also was confirmed using immunofluorescence microscopy, suggesting that NETosis plays a role in innate immunity in canine sepsis. To investigate whether canine platelets express functional TLR4, we first assessed Toll-like receptor 4 (TLR4) expression on the platelet surface in either unstimulated or activated platelets using flow cytometry. We then assessed LPS-induced platelet activation in the presence or absence of TLR4 inhibition by measuring P-selectin expression and TxB2 generation using flow cytometry and ELISA, respectively. Canine platelets had low and variable expressions of surface TLR4, which was significantly upregulated following ADP or thrombin stimulation. Platelet activation in response to LPS was limited but was significantly potentiated in platelets primed with ADP. Platelet TLR4 in dogs was shown to be active by a function blocking TLR-4 antibody or by LPS from Rhodobacter sphaeroides (LPS-RS), which significantly attenuated LPS-induced P-selectin expression in ADP-primed platelets. Inhibition of TxA2 generation with acetylsalicylic acid also modulated LPS-induced P-selectin expression suggesting that TxA2 serves as a positive feedback mediator in platelet activation during canine sepsis. Based on these findings, it was concluded that canine neutrophils produce NETs in sepsis and platelet activation via TLR4 may play a role in mediating NETosis.

Promyelocyte HL-60 Cell-line Demonstrates the Involvement of NETosis-Related Proteins in Neutrophil Nuclear Morphology Dynamics

Promyelocyte HL-60 Cell-line Demonstrates the Involvement of NETosis-Related Proteins in Neutrophil Nuclear Morphology Dynamics
A Book

by Laura Marie Waters

  • Publisher : Unknown Publisher
  • Release : 2018
  • Pages : 46
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Neutrophils are characterized by a unique nuclear morphology, where the nucleus possesses a segmented multi-lobed form. During inflammation, neutrophils become activated and utilize their anti-microbial abilities. Neutrophil activation and extracellular trap formation are associated with the cell undergoing a change in nuclear morphology via delobing of the nucleus. While much work has been done concerning which parts of the activation pathway are required for NETosis, little is known about which portions of the activation pathway are involved with these morphology dynamics. Using quantitative image analysis, we established the promyelocyte HL-60 cell-line as a model system in which to study human neutrophil nuclear morphology dynamics and differentiated HL-60s as a model to investigate activation-induced nuclear morphological changes. We find that ATRA differentiated HL-60s and DMF differentiated HL-60s can be used to observe changes in the measured circularity of the nucleus induced by PMA and A23187 stimulation respectively. Using chemical inhibitors in differentiated HL-60 stimulation, it was discovered that NOX and NE activity are required for PMA-induced nuclear morphological change while MPO and PAD4 activity are not, and that PAD4 activity is required for A23187-induced nuclear morphological change. These findings demonstrate how factors that are known to contribute to NETosis also contribute to pre-NETosis neutrophil nuclear dynamics.

The Role of Galectin-3-mediated NETosis in Systemic Lupus Erythematosus

The Role of Galectin-3-mediated NETosis in Systemic Lupus Erythematosus
A Book

by 陳璟儀

  • Publisher : Unknown Publisher
  • Release : 2017
  • Pages : 39
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Physical Phenotyping of Neutrophil NETosis Using Fluorescence-Imaging Deformability Cytometry

Physical Phenotyping of Neutrophil NETosis Using Fluorescence-Imaging Deformability Cytometry
A Book

by Hector Enrique Munoz

  • Publisher : Unknown Publisher
  • Release : 2020
  • Pages : 176
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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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.

Neutrophil Functions in Host Immunity, Inflammation and Tissue Repair

Neutrophil Functions in Host Immunity, Inflammation and Tissue Repair
A Book

by Felix Ellett,Philip Michael Elks,Sonja Vermeren

  • Publisher : Frontiers Media SA
  • Release : 2022-01-19
  • Pages : 129
  • ISBN : 2889740927
  • Language : En, Es, Fr & De
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Damage-Associated Molecular Patterns in Human Diseases

Damage-Associated Molecular Patterns in Human Diseases
Volume 1: Injury-Induced Innate Immune Responses

by Walter Gottlieb Land

  • Publisher : Springer
  • Release : 2018-10-09
  • Pages : 870
  • ISBN : 3319786555
  • Language : En, Es, Fr & De
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This book presents current understanding of the importance of modern immunology in the etiopathogenesis of human diseases and explores how this understanding is impacting on diagnosis, prognosis, treatment, and prophylaxis. As the core of modern immunology, the “danger/injury model” is introduced and addressed throughout the book. Volume I of the book describes the network of damage-associated molecular pattern molecules (DAMPs) and examines the central role of DAMPs in cellular stress responses and associated regulated cell death, the promotion and resolution of inflammation, the activation of innate lymphoid cells and unconventional T cells, the stimulation of adaptive immunity, and tissue repair. The significance of DAMPs in a wide range of human diseases will then be explored in Volume II of the book, with discussion of the implications of injury-induced innate immunity for present and future treatments. This book is written for professionals from all medical and paramedical disciplines who are interested in the introduction of innovative data from immunity and inflammation research into clinical practice. The readership will include practitioners and clinicians such as hematologists, rheumatologists, traumatologists, oncologists, intensive care anesthetists, endocrinologists such as diabetologists, psychiatrists, neurologists, pharmacists, and transplantologists.

NLRP3 Inflammasome: Regulatory Mechanisms, Role in Health and Disease and Therapeutic Potential

NLRP3 Inflammasome: Regulatory Mechanisms, Role in Health and Disease and Therapeutic Potential
A Book

by Kuo-Feng Hua,Oleg Chernikov,Ann Chen,Jong-Seok Moon

  • Publisher : Frontiers Media SA
  • Release : 2021-11-08
  • Pages : 129
  • ISBN : 2889716023
  • Language : En, Es, Fr & De
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Skin Autoimmunity

Skin Autoimmunity
A Book

by Ralf J. Ludwig,Katja Bieber,Christian David Sadik,Michael P. Schön,Gang Wang,Karin Loser

  • Publisher : Frontiers Media SA
  • Release : 2021-05-25
  • Pages : 129
  • ISBN : 2889668096
  • Language : En, Es, Fr & De
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NEC is a NETs dependent process and markers of NETosis are predictive of NEC in mice and humans

NEC is a NETs dependent process and markers of NETosis are predictive of NEC in mice and humans
A Book

by Deirdre Kathleen Vincent

  • Publisher : Unknown Publisher
  • Release : 2020
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Bacterial Virulence

Bacterial Virulence
Basic Principles, Models and Global Approaches

by Philippe Sansonetti

  • Publisher : John Wiley & Sons
  • Release : 2010-04-05
  • Pages : 320
  • ISBN : 3527323260
  • Language : En, Es, Fr & De
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Starting with basic principles, this reference and handbook discusses examples of the most advanced models of bacterial infection with regard to their value as paradigms to understand the molecular cross-talks between microbes and their host and tissue targets. It adopts a very forward-looking, advanced approach, placing special emphasis on the main global challenges facing scientists today, such as pathogenicity vs. commensalisms, infections in immunocompromised hosts and species specificity issues.

On the Role of Neutrophils and NETosis in Acute Pancreatitis

On the Role of Neutrophils and NETosis in Acute Pancreatitis
(de Neutrophilis NETosique Ad Pancreatitim Acutam Pertinentibus)

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2020
  • Pages : 129
  • ISBN : 9789176199817
  • Language : En, Es, Fr & De
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Gram-Positive Pathogens

Gram-Positive Pathogens
A Book

by Vincent A. Fischetti,Richard P. Novick,Joseph J. Ferretti,Daniel A. Portnoy,Mirian Braunstein,Julian I. Rood

  • Publisher : John Wiley & Sons
  • Release : 2019-10-01
  • Pages : 129
  • ISBN : 1683672879
  • Language : En, Es, Fr & De
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Gram-positive bacteria, lacking an outer membrane and related secretory systems and having a thick peptidoglycan, have developed novel approaches to pathogenesis by acquiring (among others) a unique family of surface proteins, toxins, enzymes, and prophages. For the new edition, the editors have enhanced this fully researched compendium of Gram-positive bacterial pathogens by including new data generated using genomic sequencing as well as the latest knowledge on Gram-positive structure and mechanisms of antibiotic resistance and theories on the mechanisms of Gram-positive bacterial pathogenicity. This edition emphasizes streptococci, staphylococci, listeria, and spore-forming pathogens, with chapters written by many of the leading researchers in these areas. The chapters systematically dissect these organisms biologically, genetically, and immunologically, in an attempt to understand the strategies used by these bacteria to cause human disease. “This textbook comprises a superb collection of scientific knowledge making it a must-read for any graduate student, medical doctor, or investigator studying these gram-positive bacteria and inspiring future imaginations of biological knowledge.” - William R. Jacobs, Jr., PhD, Professor Microbiology & Immunology, Albert Einstein College of Medicine

Role of Neutrophils in Disease Pathogenesis

Role of Neutrophils in Disease Pathogenesis
A Book

by Maitham Khajah

  • Publisher : BoD – Books on Demand
  • Release : 2017-06-07
  • Pages : 180
  • ISBN : 9535131958
  • Language : En, Es, Fr & De
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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.

Autophagy Networks in Inflammation

Autophagy Networks in Inflammation
A Book

by Maria Chiara Maiuri,Daniela De Stefano

  • Publisher : Springer
  • Release : 2016-08-17
  • Pages : 403
  • ISBN : 3319300792
  • Language : En, Es, Fr & De
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Autophagy principally serves an adaptive function to protect organisms against diverse human pathologies, including cancer and neurodegeneration. Recent developments using in vitro, ex vivo and in vivo models show the involvement of the autophagy pathway in immunity and inflammation. Moreover, direct interactions between autophagy proteins and immune signalling molecules have also been demonstrated. Defects in autophagy - similar to cancer, neurodegenerative diseases and aging - through autophagy gene mutation and/or microbial antagonism, may underlie the pathogenesis of many infectious diseases and inflammatory syndromes. In spite of the increasing awareness of the importance of autophagy in these pathophysiological conditions, this process remains underestimated and is often overlooked. As a consequence, its role in the initiation, stability, maintenance, and progression of these diseases are still poorly understood. This book reviews the recent advances regarding the functions of the autophagy pathway and autophagy proteins in immunity and inflammation, focusing on their role in self-nonself distinction, their implications in innate and adaptive immune responses and their dysregulation in the pathology of certain inflammatory and autoimmune diseases.

Apoptosis and Beyond, 2 Volume Set

Apoptosis and Beyond, 2 Volume Set
The Many Ways Cells Die

by James A. Radosevich

  • Publisher : Wiley-Blackwell
  • Release : 2018-12-18
  • Pages : 784
  • ISBN : 1119432421
  • Language : En, Es, Fr & De
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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.

Advanced Trauma and Surgery

Advanced Trauma and Surgery
A Book

by Xiaobing Fu,Liangming Liu

  • Publisher : Springer
  • Release : 2016-11-15
  • Pages : 452
  • ISBN : 9811024251
  • Language : En, Es, Fr & De
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This book discusses different aspects of trauma surgery, ranging from the various types of trauma and their management, infection, sepsis and inflammation to tissue injury and repair in trauma. It discusses cellular, molecular and genetic research findings and their role in pathogenesis in trauma and injury. In addition, it highlights the translational application of advanced theories and technologies in the management of trauma patients. This book is a valuable resource for anyone involved in the management of severe trauma damage to tissues wanting to reduce early mortality and improve patients' quality of life.

Neutrophil Communication

Neutrophil Communication
A Book

by Christian Jan Lood,Rohit Jain,Marco A. Cassatella,Jason S. Knight

  • Publisher : Frontiers Media SA
  • Release : 2020-06-29
  • Pages : 129
  • ISBN : 2889638103
  • Language : En, Es, Fr & De
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