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The microcirculation is highly responsive to, and a vital participant in, the inflammatory response. All segments of the microvasculature (arterioles, capillaries, and venules) exhibit characteristic phenotypic changes during inflammation that appear to be directed toward enhancing the delivery of inflammatory cells to the injured/infected tissue, isolating the region from healthy tissue and the systemic circulation, and setting the stage for tissue repair and regeneration. The best characterized responses of the microcirculation to inflammation include impaired vasomotor function, reduced capillary perfusion, adhesion of leukocytes and platelets, activation of the coagulation cascade, and enhanced thrombosis, increased vascular permeability, and an increase in the rate of proliferation of blood and lymphatic vessels. A variety of cells that normally circulate in blood (leukocytes, platelets) or reside within the vessel wall (endothelial cells, pericytes) or in the perivascular space (mast cells, macrophages) are activated in response to inflammation. The activation products and chemical mediators released from these cells act through different well-characterized signaling pathways to induce the phenotypic changes in microvessel function that accompany inflammation. Drugs that target a specific microvascular response to inflammation, such as leukocyte-endothelial cell adhesion or angiogenesis, have shown promise in both the preclinical and clinical studies of inflammatory disease. Future research efforts in this area will likely identify new avenues for therapeutic intervention in inflammation. Table of Contents: Introduction / Historical Perspectives / Anatomical Considerations / Impaired Vasomotor Responses / Capillary Perfusion / Angiogenesis / Leukocyte-Endothelial Cell Adhesion / Platelet-Vessel Wall Interactions / Coagulation and Thrombosis / Endothelial Barrier Dysfunction / Epilogue / References
Leukocytes play an integral role in the pathogenesis of different inflammatory disorders. Recent results indicate that leukocytes are also involved in conditions that had not formerly been associated with a cytotoxic effect by leukocytes. In 27 chapters by leading investigators, this book reviews recent research on leukocyte adhesion and microvascular kinetics. Detailed descriptions of adhesive glycoproteins expressed on the surface of leukocytes and endothelial cells are given together with summaries of the current state of leukocyte rheology, kinetics and entrapment in microvessels. Since leukocytes reach all organs, the mechanisms described in this volume may apply to a wide range of cardiovascular disorders. A variety of important inflammatory and circulatory disorders are discussed including cerebral and coronary ischemia, shock, atherogenesis, chronic venous insufficiency, gastric ulcer and diabetic retinopathy. New concepts about the etiology of cardiovascular complications are presented, with emphasis on molecular, cellular, and microvascular mechanisms. The current state of endogenous anti-adhesive and pro-adhesive mediators is summarized, including interventions against leukocyte activation and adhesion.
Leukocyte adhesion molecules have been the subject of intense basic and preclinical research. Results from clinical trials obtained sofar with antibodies directed towards these surface proteins offer promise for the prevention of graft rejection and effective treatment of acute and chronic inflammatory disease. This volume presents a comprehensive review of contemporary research on the structure, function and regulation of leukocyte adhesion molecules and their ligands, from the molecular to the clinical level. The blend of basic science and clinical applications presented in Structure, Function and Regulation of Molecules Involved in Leukocyte Adhesion provides clear evidence of the biological importance of cell-cell interactions and the many potential clinical dividends afforded by understanding the molecular basis of cell adhesion. It will appeal to a broad range of readers in immunology and cell biology.
This volume of Current Topics in Microbiology and Immunology was planned in parallel with an EM BO workshop on cell-cell Interactions in Leukocyte Homing and Differentiation held at the Basel Institute for Immunology in November 1992, and many of the workshop speakers have contributed to it. Cell adhesion is one of the most dynamic fields of biological research and presented in this book is the current knowledge on the structure and function of the major families of cell adhesion molecules-the integrins, the selectins, the immunoglobulin superfamily, and CD44. Complex interactions between the members of these families mediate diverse adhesion functions, including leukocyte-leukocyte interactions, lymphocyte homing, inflammation, and lymphocyte-stromal cell interaction during hematopoiesis. A great deal of emphasis is placed on the regulatory elements that control the expression and function of adhesion molecules. Cytokines not only induce the expression of certain adhesion molecules, but may also modify their functional status. For instance, the integrins exist in either an inactive nonfunctional form or an active functional form, and a number of intracellular or extracellular stimuli modify integrin function. This is particularly important during leukocyte binding to endothelium and transendothelial migration, which proceeds through a cascade of adhesion events. Although cell adhesion molecules play an important role in many processes, this book concentrates on their role within the immune system. A number of chapters discuss the migration of lymphocytes between hematopoietic organs such as the thymus, lymph nodes, Peyer's patches, and spleen.
Leucocyte Adhesion provides a systematic, comprehensive, and rigorous approach to specific topics relevant to the study of cellular membranes. This volume provides a review of the latest developments in leukocyte adhesion. Regulation of cell adhesion is important for immune system function. Contributions from leading experts in the field Reviews the latest developments
Leukocyte adhesion molecules promise to be highly effective as antigens in the antibody-directed leucocyte elimination treatment prior to grafting or in cases of acute and chronic inflammatory disease. This comprehensive review of contemporary research provides thorough discussions of the structure of these molecules, their in vitro function, and the role that they play in vivo as evidenced by results shown in inflammatory models where antibodies against these molecules are given to inhibit their function. The blend of basic science and clinical applications provides clear evidence of the biological relevance of cell-cell interactions and the many potential clinical dividends afforded by understanding the molecular basis of cell adhesion.
This book presents a case history of a patient with leukocyte adhesion deficiency to illustrate essential points about the mechanisms of immunity and to explain some of the immunological problems often seen in the clinic. It is helpful for medical and pre-medical students.
The Nordisk Foundation Symposia Series are organized by Nordisk Insulin Foundation Committee, which supports research projects within physiology and clinical endocrinology in the Nordic countries. The committee consists of 10 members representing basic and clinical research. The committee and resulting series was set up with a view to reviewing front topics within biomedical research of special interest to the committee. This publication is the proceedings of the Sixth symposium in the series, and was organized with a view to critically reviewing the molecular and clinical advances that recently have taken place in the understanding of leukocyte adhesion. It is hoped that this symposium and publication of its proceedings will result in a better understanding of the field and serve to define topics needing further investigation, generate new approaches and establish and strengthen personal contacts and cooperation.
This volume gives a comprehensive overview on the most relevant leukocyte and endothelial adhesion molecules. The chapters are written by leaders in the field and focus on the biology, structure, function, and regulation of adhesion molecules. Currently approved adhesion molecule-based therapies are reviewed and an outlook for future approaches is also provided. The book is of interest to clinicians and scientists from immunology, physiology, cancer research, rheumatology, allergology, infectious diseases, gastroenterology, pulmonology and cardiology.
The book will provide an overview of the roles of vascular adhesion molecules in health and disease, with chapters on their cell biology, followed by chapters reviewing their importance in specific disease processes. Vascular adhesion molecules are vital for the physiological processes of leukocyte trafficking and also critically involved in the enhanced leukocyte emigration that is a key feature of all inflammatory and immune diseases. The book is designed to provide up-to-date, linked reviews of the subject suitable for postgraduate students entering the field or research workers from allied disciplines needing a modern overview.