Macrophages are core components of the innate immune system. Once activated, they may have either pro- or anti-inflammatory effects that include pathogen killing, safe disposal of apoptotic cells or tissue renewal. The activation state of macrophages is conceptualized by the so-called M1/M2 model of polarization. M2 macrophages are not simply antagonists of M1 macrophages; rather, they represent a network of tissue resident macrophages with roles in tissue development and organ homeostasis. M2 macrophages govern functions at the interfaces of immunity, tissue development and turnover, metabolism, and endocrine signaling. Dysfunction in M2 macrophages can ruin the healthy interplay between the immune system and metabolic processes, and lead to diseases such as insulin resistance, metabolic syndrome, and type 1 and 2 diabetes mellitus. Furthermore, M2 macrophages are essential for healthy tissue development and immunological self-tolerance. Worryingly, these functions of M2 macrophages can also be disrupted, resulting in tumor growth and autoimmunity. This book comprehensively discusses the biology of M2 macrophages, summarizes the current state of knowledge, and highlights key questions that remain unanswered.
Macrophages are core components of the innate immune system. Once activated, they may have either pro- or anti-inflammatory effects that include pathogen killing, safe disposal of apoptotic cells or tissue renewal. The activation state of macrophages is conceptualized by the so-called M1/M2 model of polarization. M2 macrophages are not simply antagonists of M1 macrophages; rather, they represent a network of tissue resident macrophages with roles in tissue development and organ homeostasis. M2 macrophages govern functions at the interfaces of immunity, tissue development and turnover, metabolism, and endocrine signaling. Dysfunction in M2 macrophages can ruin the healthy interplay between the immune system and metabolic processes, and lead to diseases such as insulin resistance, metabolic syndrome, and type 1 and 2 diabetes mellitus. Furthermore, M2 macrophages are essential for healthy tissue development and immunological self-tolerance. Worryingly, these functions of M2 macrophages can also be disrupted, resulting in tumor growth and autoimmunity. This book comprehensively discusses the biology of M2 macrophages, summarizes the current state of knowledge, and highlights key questions that remain unanswered.
Macrophages have unique and diverse functions necessary for survival. And, in humans (and other species), they are the most abundant leukocytes in tissues. The Innate functions of macrophages that are best known are their unusual ability to either “Kill” or “Repair”. Since killing is a destructive process and repair is a constructive process, it was stupefying how one cell could exhibit these 2 polar – opposite functions. However, in the late 1980’s, it was shown that macrophages have a unique ability to enzymatically metabolize Arginine to Nitric Oxide (NO, a gaseous non – specific killer molecule) or to Ornithine (a precursor of polyamines and collagen for repair). The dual Arginine metabolic capacity of macrophages provided a functional explanation for their ability to kill or repair. Macrophages predominantly producing NO are called M1 and those producing Ornithine are called M2. M1 and M2 – dominant responses occur in lower vertebrates, and in T cell deficient vertebrates being directly driven by Damage and Pathogen Associated Molecular Patterns (DAMP and PAMP). Thus, M1 and M2 are Innate responses that protect the host without Adaptive Immunity. In turn, M1/M2 is supplanting previous models in which T cells were necessary to “activate” or “alternatively activate” macrophages (the Th1/Th2 paradigm). M1 and M2 macrophages were named such because of the additional key findings that these macrophages stimulate Th1 and Th2 – like responses, respectively. So, in addition to their unique ability to kill or repair, macrophages also govern Adaptive Immunity. All of the foregoing would be less important if M1 or M2 – dominant responses were not observed in disease. But, they are. The best example to date is the predominance of M2 macrophages in human tumors where they act like wound repair macrophages and actively promote growth. More generally, humans have become M2 – dominant because sanitation, antibiotics and vaccines have lessened M1 responses. And, M2 dominance seems the cause of ever - increasing allergies in developed countries. Obesity represents a new and different circumstance. Surfeit energy (e.g., lipoproteins) causes monocytes to become M1 dominant in the vessel walls causing plaques. Because M1 or M2 dominant responses are clearly causative in many modern diseases, there is great potential in developing the means to selectively stimulate (or inhibit) either M1 or M2 responses to kill or repair, or to stimulate Th1 or Th2 responses, depending on the circumstance. The contributions here are meant to describe diseases of M1 or M2 dominance, and promising new methodologies to modulate the fungible metabolic machinery of macrophages for better health.
Monocytes represent one of the major types of white blood cells in man which prevent infection by ingesting and killing invading pathogens and by releasing factors which stimulate and regulate lymphocytes. Monocytes "purify" the blood, removing immune complexes, mediating inflammatory responses, and initiating tissue repair. Human Monocytes represents an up-to-date, definitive account of this important cell. It covers the cells biochemical, immunological, and inflammatory functionsand its role in many diseases, including asthma, atherosclerosis, rheumatoid arthritis, and AIDS.
The world is faced with an epidemic of metabolic diseases such as obesity and type 2 diabetes. This is due to changes in dietary habits and the decrease in physical activity. Exercise is usually part of the prescription, the first line of defense, to prevent or treat metabolic disorders. However, we are still learning how and why exercise provides metabolic benefits in human health. This open access volume focuses on the cellular and molecular pathways that link exercise, muscle biology, hormones and metabolism. This will include novel “myokines” that might act as new therapeutic agents in the future.
Biomaterials have existed for millennia as mechanical replacement structures following disease or injury. Biomaterial design has changed markedly from structural support with an "inert immune profile as the primary objective to designs that elicit an integrative local tissue response and a pro-repair immune cell phenotype. Immunomodulatory Biomaterials: Regulating the Immune Response with Biomaterials to Affect Clinical Outcome offers a single, comprehensive reference on biomaterials for modulation of the host response, for materials scientists, tissue engineers and those working in regenerative medicine. This book details methods, materials and strategies designed to regulate the host immune response following surgical implantation and thus facilitate specific local cell infiltration and tissue deposition. There has been a dramatic transformation in our understanding of the role of the immune system, both innate and adaptive; these changes include recognition of the plasticity of immune cells, especially macrophages, cross-talk between the immune system and stem cells, and the necessity for in situ transition between inflammatory and regulatory immune cell phenotypes. The exploitation of these findings and the design and manufacture of new biomaterials is occurring at an astounding pace. There is currently no book directed at the interdisciplinary principles guiding the design, manufacture, testing, and clinical translation of biomaterials that proactively regulate the host tissue immune response. The challenge for academia, industry, and regulatory agencies to encourage innovation while assuring safety and maximizing efficacy has never been greater. Given the highly interdisciplinary requirements for the design, manufacture and use of immunomodulatory biomaterials, this book will prove a useful single resource across disciplines. - Holistically covers the design, manufacture, testing, and clinical translation of biomaterials that proactively regulate the host tissue immune response - Provides a single reference for understanding and utilizing the host response in biomaterials design - An international collaboration of leading researchers in the field offering a novel insight into this fast-growing area
“Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists...). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.
In light of the critical contributions of macrophages and dendritic cells to diverse inflammatory diseases and to immunity and host defense, state-of-the-art approaches to the investigation of their behavior are essential. In Macrophages and Dendritic Cells: Methods and Protocols, expert researchers contribute laboratory protocols involving these two vital cell types functioning at the junction of the innate and acquired immune systems. The volume delves first into isolation and cell culturing then continues with topics such as phagocytosis, genetic manipulation, macrophage activation, and lipid signaling. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include brief introductions to their respective subjects, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Macrophages and Dendritic Cells: Methods and Protocols provides a timely and useful guide for both seasoned investigators and neophytes pursuing this imperative field of study.
Dieses Fachbuch erläutert die molekularen Grundlagen von Entzündungen, spannt den Bogen zu Infektionskrankheiten und den Zusammenhang zwischen Entzündungen und chronischen Erkrankungen, behandelt abschließend den Heilungsprozess und zeigt Therapiemöglichkeiten.
The generation of tridimensional tissues, assembled from scaffolding materials populated with biologically functional cells, is the great challenge and hope of tissue bioengineering and regenerative medicine. The generation of biomaterials capable of harnessing the immune system has been particularly successful. This book provides a comprehensive view of how immune cells can be manipulated to suppresses inflammation, deliver vaccines, fight cancer cells, promote tissue regeneration or inhibit blood clotting and bacterial infections by functionally engineered biomaterials. However, long-lived polymers, such as those employed in orthopedic surgery or vascular stents, can often induce an immune reaction to their basic components. As a result, this book is also an important step towards coming to understand how to manipulate biomaterials to optimize their beneficial effects and downplay detrimental immune responses.