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

This reference is a volume in the Handbook of Physiology, co-published with The American Physiological Society. Growth in knowledge about the microcirculation has been explosive with the field becoming fragmented into numerous subdisciplines and subspecialties. This volume pulls all of the critical information into one volume. - Meticulously edited and reviewed. Benefit: Provides investigators a unique tool to explore the significance of their findings in the context of other aspects of the microcirculation. In this way, the updated edition has a direct role in helping to develop new pathways of research and scholarship - Highlights the explosive growth in knowledge about the microcirculation including the biology of nitric oxide synthase (NOS), endothelial cell signaling, angiogenesis, cell adhesion molecules, lymphocyte trafficking, ion channels and receptors, and propagated vasomotor responses. Benefit: Microcirculatory biology has become fragmented into numerous sub-disciplines and subspecialties, and these reference reintegrates the information in one volume

Mast Cells and Basophils will be essential reading for immunologists, biochemists and medical researchers. Detailed chapters cover all aspects of mast cell and basophil research, from cell development, proteases, histamine, cysteinyl leukotrienes, physiology and pathology to the role of these cells in health and disease. Chapters also discuss the clinical implications of histamine receptor antagonists.

The book describes how the balance between pro- and anti-inflammatory molecules is related to health and disease. It is suggested that many diseases are initiated and their progress is influenced by inflammatory molecules and a decrease in the production and/or action of anti-inflammatory molecules and this imbalance between pro- and anti-inflammatory molecules seems to have been initiated in the perinatal period. This implies that strategies to prevent and manage various adult diseases should start in the perinatal period. An alteration in the metaolism of essential fatty acids and their anti-inflammatory molecules such as lipoxins, resolvins, protecitns, maresins and nitrolipids seems to play a major role in the pathobiology of several adult diseases. Based on these concepts, novel therapeutic approaches in the management of insulin resistance, obesity, type 2 diabetes mellitus, metabolic syndrome, cancer, lupus, rheumatoid arthritis and other auto-immune diseases are presented. Based on all these evidences, a unified concept that several adult diseases are due to an alteration in the balance between pro- and anti-inflammatory molecules is discussed and novel methods of their management are presented.

Arrest chemokines are a small group of chemokines that promote leukocyte arrest from rolling by triggering rapid integrin activation. Arrest chemokines have been described for neutrophils, monocytes, eosinophils, naïve lymphocytes and effector memory T cells. Most arrest chemokines are immobilized on the endothelial surface by binding to heparin sulfate proteoglycans. Whether soluble chemokines can promote integrin activation and arrest is controversial (Alon-Gerszten). Many aspects of the signaling pathway from the GPCR chemokine receptor to integrin activation are the subject of active investigation. Leukocyte adhesion deficiency III is a human disease in which chemokine-triggered integrin activation is defective because of a mutation in the cytoskeletal protein kindlin-3. About 10 different such mutations have been described. The defects seen in patients with LAD-III elucidate the importance of rapid integrin activation for host defense in humans. We welcome reports that help clarifying this crucial first step in the process of leukocyte transendothelial migration.

The third book in the group devoted to the "natural" immune system, this volume provides the ideal detailed, up-to-date overview of neutrophil function. Distilling new information alongside observations of the past, the book focuses on some of the most critical developments in currentneutrophil research. Specific examples of diseases resulting from neutrophil dysfunction and deficiency are brought to life by clinical case studies. An essential source of current research into this exciting field, this volume will be invaluable for advanced students and researchers in immunology,cell biology, and medicine.

Immune Rebalancing: The Future of Immunosuppression summarizes the most promising perspectives of immunopharmacology, in particular in the area of immunosuppression by considering molecular pathways, personalized medicine, microbiome and nanomedicine. Modulation of immune responses for therapeutic purposes is a particularly relevant area, given the central role of anomalous immunity in diseases. These diseases vary from the most typically immune-related syndromes (autoimmune diseases, allergy and asthma, immunodeficiencies) to those in which altered immunity and inflammation define the pathological outcomes (chronic infections, tumours, chronic inflammatory and degenerative diseases, metabolic disorders, etc. - Visits immunosuppression from a modern point of view of signalling mechanisms at the light of the current knowledge of signalling mechanisms and regulatory networks allows the reader to formulate new ideas and concepts on how to use immunosuppression the therapeutic purposes - Encourages researchers to engage into exploring the field of pharmacological modulation of immune responses in depth, and with the new knowledge and tools available, designs more effective therapeutic strategies to autoimmune and inflammatory diseases, cancer, degenerative diseases and infections - Examines the link between molecular pathways associated to immune-suppression and the new immunopharmacology approaches - Provides information on the new strategies for drug development in this field - Considers the role of microbes in the development of the mammalian immune system and immune responses, which will widen the reader's strategy for addressing therapeutic immune modulations

This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.