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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.
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.
The complex and critical process of extracellular matrix (ECM) assembly is described in this book. Assembly may involve molecules interacting with molecules of the same matrix class, such as in collagen, or interactions between different ECM molecules, such as in basement membranes. The text shows how this is driven by structural information within the matrix monomer. This information will be of interest to cell, developmental, and molecular biologists, biochemists, biophysicists, and biomedical researchers involved in macromolecular assembly, biological macromolecules, and extracellular matrix. - Addresses assembly of most of the known classes of extracellular matrix macromolecules - Discusses higher order structures produced by ECM - Gives important concepts in ECM and cell-matrix interactions, Protein structure and protein-protein interactions, Development and tissue remodeling
An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.
This Volume of the series Cardiac and Vascular Biology offers a comprehensive and exciting, state-of-the-art work on the current options and potentials of cardiac regeneration and repair. Several techniques and approaches have been developed for heart failure repair: direct injection of cells, programming of scar tissue into functional myocardium, and tissue-engineered heart muscle support. The book introduces the rationale for these different approaches in cell-based heart regeneration and discusses the most important considerations for clinical translation. Expert authors discuss when, why, and how heart muscle can be salvaged. The book represents a valuable resource for stem cell researchers, cardiologists, bioengineers, and biomedical scientists studying cardiac function and regeneration.
Macrophages were initially identified as a key element in the innate host response to infection and injury due to their phagocytic clearance and elimination of pathogenic and non-pathogenic entities. However, as macrophage research advanced it became clear that not only are these cells amenable to the acquisition of multiple plastic phenotypes during inflammatory responses to different pathogens, they also play a paramount role in the termination of inflammation and acquired immune responses. In addition, macrophages profoundly affect host physiology when they migrate to distant sites and differentiate to specialized cells, like foam cells, osteoclasts, adipose tissue- and tumor -associated macrophages and other macrophage-derived cell types. These processes are affected by the inflammation-resolution axis and can result in health threats, such as atherosclerosis, bone loss, obesity, fibrosis and cancer. This Research Topic issue will cover a wide range of topics in macrophage biology: 1. Macrophages in immune responses to pathogens 2. Macrophages in the termination of acute and acquired immunity. 3. The role of macrophages and their descendents in inflammation-associated pathologies. 4. Macrophage polarization and differentiation. Particular focus will be given to the modulation of macrophage phenotype and function following their encounter with apoptotic cells and the signaling cascades that govern these changes.