Cellular and Molecular Aspects of Inflammation

I. Cellular Interactions in Inflammatory Processes.- 1 Cellular Interactions Regulating Inflammation: Activation of T Lymphocytes at Inflammatory Sites and Their Role in Perpetuating Chronic Inflammation.- 1. Introduction.- 2. Antigen-Induced T Cell Activation.- 3. Cellular Interactions Involved in the Initiation of T Cell Activation.- 4. CD2, CD11a, and HLA-A, B, C Molecules Are Involved in T Cell-Accessory Cell Interactions that Promote T Cell Responses.- 5. The Role of CD 5 and CD 28 in T Cell Activation.- 6. The Role of CD4 in T Cell Proliferation.- 7. Proposed Model of the Signals Involved in T Cell Activation.- 8. Conclusions.- References.- 2 Triggering and Activation of Human Neutrophils: Two Aspects of the Response to Transmembrane Signals.- 1. Phospholopid Remodeling and Intracellular Messengers.- 2. Phospholipase A Activation in Neutrophils.- 3. Arachidonate Metabolism.- References.- 3 Neutrophil Emigration: Quantitation, Kinetics, and the Role of Mediators.- 1. Introduction.- 2. Quantitation and Kinetics.- 3. Mediators of Neutrophil Emigration.- 4. Conclusions.- References.- 4 The Role of Endothelium in Chronic Inflammation.- 1. Introduction.- 2. Lymphocyte-Rich and Transitional Areas of Synovial Membrane and Lymph Node.- 2.1. Steps in Lymphocyte Emigration.- 2.2. T Cell to Endothelial Cell Binding.- 2.3. Effect of Cytokines on T Cell to Endothelial Cell Binding.- 2.4. Effect of Lipopolysaccharide on T Cell to Endothelial Cell Binding.- 2.5. Chemotaxis in the Emigration of Lymphocytes from the Postcapillary Venule.- 2.6. Production of IL-1 by Human Endothelial Cells.- 2.7. Mechanisms of T Cell-Endothelial Cell Interaction.- 3. Discussion.- References.- II. Peptide Mediators of Inflammation.- 5 Peptide Mediators of Inflammation: An Overview.- 6 Interleukin-1: Biology and Molecular Biology.- 1. Introduction.- 2. IL-1 and T Cell Activation.- 3. IL-1 Receptor Studies.- 4. IL-1 Secretion and Extracellular Processing.- 5. Membrane IL-1.- 6. IL-1 and Inflammatory Cells.- 7. Unanswered Questions.- References.- 7 Structure-Function Relations for the Interleukin-2 Receptor.- 1. A Molecular Explanation for the Different Affinities of the IL-2 Receptor.- 1.1. High-and Low-Affinity IL-2 Binding Sites: Role of the Tac (Alpha) Protein.- 1.2. The Two-Chain Hypothesis for the High-Affinity IL-2 Receptor.- 1.3. Characterization of a Novel IL-2 Binding Molecule (Beta).- 1.4. Evidence that High-Affinity Binding Is the Result of an Alpha-IL-2-Beta Complex.- 2. Multiple Forms of the IL-2 Receptor: Function and Cellular Distribution.- 2.1. Type I Receptors: The Alpha (Tac) Chain.- 2.2. Type II Receptors: The Beta Chain.- 2.3. Type III Receptors: The Alpha-IL-2-Beta Complex.- 3. Ligand Binding and the Structure of the Tac Receptor Protein.- 3.1. Localization of the IL-2 Binding Site.- 3.2. Ligand Binding by Tac Protein Variants.- 3.3. Disulfide Structure of the Tac Protein.- 3.4. Sequence Analysis of Soluble Tac Protein.- 4. Concluding Remarks.- References.- 8 Cachectin (Tumor Necrosis Factor): A Macrophage Protein that Induces a Catabolic State and Septic Shock in Infected Animals.- 1. Introduction.- 2. The Parallel Histories of Cachectin and Tumor Necrosis Factor.- 3. Structure of the Cachectin/TNF Peptide, Message, and Gene.- 3.1. Several Mammalian Species Express Homologous Cachectins as Prohormones.- 3.2. Cachectin Genes Exhibit Potential Regulatory Features.- 4. Regulation of Expression and Correlation with Disease States.- 4.1. Bacterial, Viral, and Protozoal Stimuli Induce Cachectin.- 4.2. Dexamethasone, IFN-?, and the 1psd Mutation Regulate Cachectin.- 4.3. Characterization and Biodistribution of the Systemic Cachectin Response.- 4.4. Infusion of Cachectin Closely Mimics Endotoxemia.- 4.5. Cachectin in Disease States.- 5. Cachectin/TNF Receptor and Mechanism of Action.- 6. Biological Activities: Parallels between Disease States, in Vitro Effects, and in Vivo Models.- 6.1. Adipocytes.- 6.2. Skeletal Muscle and Muscle Cell Lines.- 6.3. Endothelial Cells, Procoagulant Activity, and Leukocyte Adhesion.- 6.4. Bone, Cartilage, and Fibroblasts.- 6.5. Liver and Hepatocytes.- 6.6. Leukocytes.- References.- III. Biosynthesis and Release of Lipid Mediators of Inflammation.- 9 Arachidonic Acid Metabolism in Tissue Injury.- 1. Introduction.- 2. Exaggerated Eicosanoid Production in Hydronephrosis.- 2.1. Arachidonic Acid Metabolism in Normal and Hydronephrotic Kidney.- 2.2. Accumulation of Inflammatory Cells in Hydronephrosis.- 2.3. Role of Tissue Macrophages.- 2.4. Monokines.- 2.5. Production of Leukotrienes in Hydronephrosis.- 3. Essential Fatty Acid Deficiency and Arachidonic Acid Metabolism in Inflammation.- 3.1. Biochemical Effects.- 3.2. Functional Effects.- 3.3. Effect of EFA Deficiency on Hydronephrosis.- 4. Arachidonic Acid Metabolism in Myocardial Infarction.- 4.1. Eicosanoid Production in Rabbit Myocardial Ischemia.- 4.2. Biochemical, Morphological, and Anatomical Considerations.- References.- 10 Lipoxygenase Metabolites: Chemistry and Biochemistry.- 1. Introduction.- 2. General Overview.- 3. Specific Examples.- 3.1. Determination of Structure and Biosynthesis: The Lipoxins.- 3.2. Analogues as Probes for Structural Specificity.- 3.3. Determination of in Vivo Metabolism of the Peptido-Leukotrienes.- 4. Conclusions.- References.- IV. Molecular Intermediates in Signal Transductions.- 11 Guanine Nucleotide Regulatory Proteins in Inflammatory and Immune Responses.- 1. Introduction.- 2. General Aspects of G-Protein Structure and Function.- 2.1. Receptor-Effector Coupling and the GTPase Cycle.- 2.2. Subunit Structure.- 2.3. Subcellular Localization.- 2.4. Effects of Bacterial Toxins.- 3. Specific G Proteins and Their Functions.- 3.1. Gs and Gi.- 3.2. Gpi.- 3.3. Other G Proteins.- 4. Molecular Biology of G-Proteins.- 5. Specificity of Receptor-Effector Coupling by G Proteins.- 6. Regulation of G Protein Function.- 7. G Proteins in Inflammatory and Immune Responses.- 7.1. G Proteins in Neutrophils.- 7.2. G Proteins in Lymphocytes and Macrophages.- 8. Conclusions.- References.- 12 Regulation of Phosphoinositide Breakdown.- 1. Introduction.- 2. Phosphoinositide Metabolism.- 3. Receptors for Calcium-Mobilizing Agonists.- 4. Role of Guanine Nucleotide Binding Proteins in Agonist Regulation of Phosphoinositide Breakdown.- 5. Growth Factors and Phosphoinositide Metabolism.- 6. Agonist-Regulated Phosphoinositide Phospholipase C.- 7. Summary.- References.- 13 Regulation of Protein Kinase C by Sphingosine/Lysosphingolipids.- 1. Introduction.- 1.1. Discovery of Protein Kinase C and sn-1, 2-Diacylglycerol Second Messengers.- 1.2. Phorbol Ester Receptor and Tumor Promotion.- 1.3. Signal Transduction: Growth Factors, Neurotransmitters, and Hormones.- 1.4. Oncogene Products and Signal Transduction.- 1.5. Scope and Content.- 2. Structure, Function, and Regulation of Protein Kinase C.- 2.1. Cell-Permeable DAGs and DAG Analogues.- 2.2. Quantitation of DAG Second Messengers.- 2.3. Cloning and Expression of Multiple Rat Brain Protein Kinase C cDNAs.- 2.4. Domain Structure of Protein Kinase C.- 2.5. Mechanism of Regulation by PS, Ca2+, DAG (Phorbol Esters): Mixed Micellar Analysis.- 3. Sphingosine/Lysosphingolipid Inhibition of Protein Kinase C.- 3.1. Inhibition in Vitro.- 3.2. Inhibition of Protein Kinase C in Cells by Sphingosine.- 3.3. Hypothesis.- References.- 14 Regulation of Inositol Trisphosphate Formation and Action.- 1. Introduction.- 2. Control of Phospholipase C.- 2.1 Guanine Nucleotides.- 2.2 Calcium.- 2.3 Receptors.- 3. Metabolism of Inositol 1,4,5-Trisphosphate.- 4. Actions of Inositol Phosphates.- 4.1 Calcium Release.- 4.2 Calcium Entry.- 5. Conclusions.- References.- V. Receptors and Signal Transduction Processes Involved in Inflammation.- 15 Molecular Properties of Leukocyte Receptors for Leukotrienes.- 1. Introduction.- 2. Specificity and Affinity of Human Leukocyte Receptors for Leukotrienes.- 3. Subcellular Distribution of Leukotriene Receptors of Human PMN Leukocytes.- 4. Structural Properties of the Leukotriene Receptors.- 5. Biochemical Transduction of Signals from Leukocyte Receptors for Leukotrienes.- 6. Antibodies to Leukotriene Receptors.- 7. Development of Leukotriene Receptors During Differentiation of Leukocytes.- 8. Clinical Implications.- References.- 16 LTD4 Receptors and Signal Transduction Processes.- 1. Introduction.- 2. The LTD4 Receptors.- 3. The Guanine Nucleotide Binding Proteins.- 4. The PI-Phospholipase C.- 5. Inositol Phosphate Metabolism.- 6. Calcium Mobilization.- 7. Protein Kinase C.- 8. Phospholipase A2 Activating Protein.- 9. 5-Lipoxygenase-LTA4 Synthetase.- 10. Epigenetic Regulation.- 11. Genetic Regulation.- 12. Conclusion.- References.- 17 Characterization of Thromboxane A2/Prostaglandin H2 Receptors.- 1. Introduction.- 2. Platelet and Vascular Thromboxane A2 Receptors.- 2.1 Pharmacologic Identification of Subclasses of Receptors.- 3. Radioligand Binding Studies.- 4. Second Messenger Systems.- 4.1. Platelets.- 4.2. Vascular Smooth Muscle.- 5. Summary.- References.- 18 Chemoattractant Receptors and Signal Transduction Processes.- 1. Introduction.- 2. Chemoattractant Receptors.- 3. Receptor/GTP-Binding protein/Phospholipase C Pathway.- 4. Characterization of the GTP-Binding Protein Involved in Leukocyte Activation.- 5. Calcium Mobilization and Inositide Metabolisn in Leukocytes.- 6. Diacylglycerol and Protein Kinase C Involvement.- 7. Termination of Chemoattractant Responses.- 8. Summary.- References.- 19 The Molecular Biology of the Human Interleukin-2 Receptor.- 1. Introduction.- 2. Identification of Anti-IL-2 Receptor Monoclonal Antibodies.- 3. IL-2 Receptor (Tac) Biosynthesis.- 4. Molecular Cloning of IL-2 Receptor (Tac) cDNAs.- 5. The IL-2 Receptor (Tac) Gene.- 6. Expression of Multiple IL-2 Receptor (Tac) mRNAs.- 7. High- and Low-Affinity Receptors for IL-2.- 8. HTLV-I, IL-2 Receptors, and the Adult T Cell Leukemia.- 9. Human Immunodeficiency Virus, Interleukin-2, and the Acquired Immune Deficiency Syndrome.- 10. Summary.- References.- VI. The Role of Phospholipases in Inflammation.- 20 Some Novel Phospholipase C Activities: Actions on Phosphatidylcholine and on Phosphatidylinositol-Glycans as Anchors for Membrane Proteins and as Precursors for Possible Insulin Mediators.- 21 Enzymatic Mechanisms and Inhibition of Phospholipase A2: From Manoalide to the Lipocortins.- 1. Introduction.- 2. Competitive Inhibitors.- 3. Irreversible Inhibitors.- 4. Lipocortins.- References.- 22 Molecular Mechanism of Regulation of Cellular Phospholipases.- 1. Introduction.- 2. Inhibition of Cellular Phospholipase(s) by Glucocorticoids.- 2.1. Inhibition of Arachidonic Acid Release.- 2.2. Properties of Lipocortins.- 2.3. Inhibition of Phospholipases by Lipocortins.- 3. Evidence for the Complex of Lipocortins with Phospholipases Inside Cells.- 3.1. Calcium and Phospholipases.- 3.2. Digestion of Lipocortins by Proteases.- 3.3. Phosphorylation of Lipocortins.- 3.4. N(G) Proteins and Lipocortins, GTP-Binding Proteins.- 4. Summary.- References.- 23 The Metabolism of Inositol Phosphates.- 1. Introduction.- 2. Phospholipase C.- 3. Substrate Specificity.- 4. Guanine Nucleotide Binding Proteins.- 5. Inositol Phosphates.- 6. Ins(I,3,4) P3and Ins(I,3,4,5)P4.- 7. Inositol Bisphosphate Metabolism.- 8. Inositol(1,4,5)P3 5-Phosphomonoesterase.- 9. Future Challenges.- References.