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Phagocytosis has been at the forefront of cell biology for more than a century. Initially, phagocytosis, which comes from Greek words meaning "devouring cells," was discovered in the late 19th century by Ilya Metchnikoff, who was awarded, together with Paul Ehrlich, the Nobel Prize in Physiology and Medicine in 1908 "in recognition of their work on immunity." At that time Metchnikoff had already identified a function for phagocytes not only in host defense but also as scavengers of degenerating host cells during metamorphosis of tadpoles, thus providing one of the first descriptions of apoptotic cell clearance by macrophages (Kaufmann 2008). Since then, much has been learned about phagocytosis, and the previous several decades have witnessed outstanding progress in understanding the functions and the molecular mechanisms of phagocytosis. Two main types of targets are cleared by phagocytosis: microbial pathogens and dying cells. Rapid recognition and clearance of dying cells by phagocytes plays a pivotal role in development, maintenance of tissue homeostasis, control of immune responses, and resolution of inflammation. Clearance of dying cells can be divided into several stages, including sensing, r- ognition, binding and signaling, internalization, and immunological responses. In this book, our contributors address these different stages of dead cell cle- ance and examine how impaired clearance of dying cells may lead to human d- eases. We have attempted to provide sufficient cross-referencing and indexing to enable the reader to easily locate the ideas elaborated in the different chapters.
This book deals with many recent advances made in uncovering the molecular and cellular basis of phagocytosis of apoptotic and necrotic dying cells as well as with the methods used for studying their clearance. There are important practical and clinical reasons for attempting to understand the molecular mechanisms of phagocytosis of dying cells, because inadequate clearance of dying cells may contribute to the development of autoimmune diseases (e.g. systemic lupus erythematosus), as well as atherosclerosis and chronic lung diseases (e.g. chronic obstructive pulmonary disease, asthma and cystic fibrosis). Furthermore, in this book we examine the possibility of using apoptotic cells in the prevention and treatment of graft rejection and in the rational design of immunotherapy and vaccines for cancer treatment. The role of environmental factors in phagocytosis of dying cells is also addressed. This comprehensive volume integrates the most innovative and current findings from several related disciplines of scientific research, including pathology, immunology, genetics, and cellular and molecular biology. It is divided into two sections: "Molecular mechanisms of phagocytosis of dying cells" and "Impairment of phagocytosis of dying cells and its role in the development of diseases." No other recent books devoted to this subject are available. All of the contributors are experts working at the forefront of scientific discovery, and the reviews they present systematically examine the most exciting and innovative aspects of their particular areas of expertise. Both researchers and physicians will find this volume of major benefit because it covers the immunological and molecular biological aspects of phagocytosis of dying cells as well as its clinical relevance.
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