This detailed volume explores the NADPH oxidase family of enzymes in human physiology and genetic disease, in which early discoveries represent prime examples of the finest translational “from bed to bench and back” studies. Methods are included for testing assembly and function of multicomponent oxidase complexes and for analyzing reactive oxygen species (ROS) generation in different systems by various means, while addressing pitfalls of ROS probes currently being used, as well as protocols on NADPH oxidase regulation and their function in cells. Written in the highly successful Methods in Molecular Biology series format, chapters include introduction to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, NADPH Oxidases: Methods and Protocols will aid researchers working with the NOX/DUOX family in continuing and expanding upon their vital research.
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
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 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.
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.
The Mosaic of Autoimmunity: The Novel Factors of Autoimmune Diseases describes the multifactorial origin and diversity of expression of autoimmune diseases in humans. The term implies that different combinations of factors in autoimmunity produce varying and unique clinical pictures in a wide spectrum of autoimmune diseases. Most of the factors involved in autoimmunity can be categorized into four groups: genetic, immune defects, hormonal and environmental factors. In this book, the environmental factors are reviewed, including infectious agents, vaccines as triggers of autoimmunity, smoking and its relationship with rheumatoid arthritis, systemic lupus erythematosus, thyroid disease, multiple sclerosis and inflammatory bowel diseases. An entirely new syndrome, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA), is also included, along with other diseases that are now recognized as having an autoimmune etiopathogenesis.
Histone Modifications in Therapy provides an in-depth analysis of the role of histone mechanisms in major diseases and the promise of targeting histone modifications for disease prevention and treatment. Here, researchers, clinicians and students will discover a thorough, evidence-based discussion of the biology of histones, the diseases engaged by aberrant histone modifications, and pathways with therapeutic potential. Expert chapter addresses the role of histone modifications across a variety of disorders, including cancer, neuropsychiatric, neurodegenerative, cardiac, metabolic, infectious, bacterial, autoimmune and inflammatory disorders, among others. In relation to these disease types, histone modifications are discussed, both as mechanisms of prevention and possible treatment. A concluding chapter brings together future perspectives for targeting histone modifications in therapy and next steps in research.
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
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.
Vascular Responses to Pathogens focuses on the growing research from leaders in the field for both the short and long-term impact of pathogens on the vasculature. It discusses various organisms, including bacteria, parasites, and viruses, and their role in key events leading to vascular disease. Formatted to discuss the topic of the interaction of pathogens with the vascular rather than individual diseases described separately, this reference demonstrates that common mechanisms are at play in many different diseases because they have a similar context, their vasculature. This all-inclusive reference book is a must-have tool for researchers and practicing clinicians in the areas of vascular biology, microvasculature, cardiology, and infectious disease. - Covers a wide spectrum of organisms and provides analysis of pathogens and current therapeutic strategies in the context of their vasculature - Provides detailed perspectives on key components contributing to vascular pathogens from leaders in the field - Interfaces between both vascular biology and microbiology by encompassing information on how pathogens affect both macro and microvasculature - Includes coverage of the clinical aspects of sepsis and current therapeutic strategies and anti-sepsis drugs
