Full Description
Chemokines and their receptors play a central role in the pathogenesis of numerous, perhaps all, acute and chronic inflammatory diseases. About 50 distinct chemokines produced by a variety cell types and tissues either c- stitutively or in response to inflammatory stimuli are involved in a plethora of biological processes. These small secreted proteins exert their exquisitely variegated functions upon binding to a family of seven-transmembrane spanning G-protein coupled receptors (GPCRs) composed of almost 20 distinct entities. The biological activities of chemokines range from the control of leukocyte trafficking in basal and inflammatory conditions to the regulation of hema- poiesis, angiogenesis, tissue architecture, and organogenesis. The basis for such diversified activities rests, on one hand, upon the ubiquitous nature of chemokine production and chemokine receptor expression. Virtually every cell type can produce chemokines and expresses a unique combination of chemokine receptors. On the other hand, chemokine receptors make use of a flexible and complex network of intracellular signaling machineries that can regulate a variety of cellular functions ranging from cell migration, growth, and differentiation to death. As knowledge of the size of chemokine and chemokine receptor families rapidly reaches completeness, much is still to be uncovered in terms of fu- tional architecture of the chemokine system. The disparity between the large number of chemokines and that smaller number of receptors is balanced by the promiscuity in ligand-receptor interactions, with multiple chemokines binding to the same receptor and several chemokines binding to more than one receptor.
Contents
Chemotaxis and Interaction with Vascular or Lymphatic Endothelium.- Analysis of Integrin-Dependent Rapid Adhesion Under Laminar-Flow Conditions.- Posttranslational Processing of Chemokines.- Chemotactic Profiling of Lymphocyte Subpopulations.- Measurement of the Levels of Polymerized Actin (F-Actin) in Chemokine-Stimulated Lymphocytes and GFP-Coupled cDNA Transfected Lymphoid Cells by Flow Cytometry.- Evaluation of Rho Family Small G-Protein Activity Induced by Integrin Ligation on Human Leukocytes.- Reconstructing Leukocyte Migration in 3D Extracellular Matrix by Time-Lapse Videomicroscopy and Computer-Assisted Tracking.- Analyzing Chemotaxis Using Dictyostelium discoideum as a Model System.- Conditional Transgenic Models to Study Chemokine Biology.- Intravital Microscopy as a Tool for Studying Recruitment and Chemotaxis.- Tracking Antigen-Specific Lymphocytes In Vivo.- Analysis of Homing-Receptor Expression on Infiltrating Leukocytes in Disease States.- Interaction of Viral Chemokine Inhibitors with Chemokines.- Discovery of Small-Molecule Antagonists of Chemokine Receptors.- Visualization and Analysis of Adhesive Events in Brain Microvessels by Using Intravital Microscopy.- Animal Models to Study Chemokine Receptor Function In Vivo.- Assessing the Role of Multiple Phosphoinositide 3-Kinases in Chemokine Signaling.- In Vitro and In Vivo Models to Study Chemokine Regulation of Angiogenesis.- Real-Time In Vitro Assay for Studying Chemoattractant-Triggered Leukocyte Transendothelial Migration Under Physiological Flow Conditions.- Generation of Monoclonal Antibodies Against Chemokine Receptors.- Detection of High-Affinity ?4-Integrin Upon Leukocyte Stimulation by Chemoattractants or Chemokines.
