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

An essential component of inflammation is the migration of circulating leukocytes from blood into tissues. This process is characterized by a multistep paradigm of sequential cell adhesion and activation events that lead to the extravasation of specific leukocyte subsets to different tissues in health and disease. The first step of leukocyte extravasation, the rolling of leukocytes, is primarily mediated by the interactions of selectins and their ligands. It has recently become evident that fucosyltransferases are crucial for selectin ligand synthesis, inflammation, and skin homing. This book provides an in-depth overview of the mechanisms of leukocyte trafficking and of the molecular mechanisms of selectin/selectin ligand interactions and discusses options for pharmacological intervention to treat inflammatory diseases.

Written by known specialists in the field, this is a comprehensive and timely overview of a central and expanding topic. Simultaneously an introduction and a description of the latest concepts, findings and methods, the handbook provides basic knowledge on technical issues required for those intending to research in the field. It covers the functional role of involved molecules and the cellular mechanisms, and addresses selected examples for their possible application in therapy -- bridging the gap between trafficking mechanisms and novel therapeutic strategies. In addition, it includes selection of proven and timesaving methods for studying cell trafficking in vitro and in vivo. The accompanying CD-ROM makes leukocyte migration videos available to a broad audience for the first time.

The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References

Entries in a practical A to Z Format Highly therapy-focused Uniform and clearly arranged entries for ease of reference Comprehensive information on symptoms and therapeutical possibilities of rheumatologic and musculoskeletal diseases as well as drugs Written by leading experts in the field