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Book Details
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Contents | v | ||
| Chapter 1 TNF Superfamily in Inflammation | 1 | ||
| 1. Introduction | 1 | ||
| 1.1. Discovery of TNF and lymphotoxin | 1 | ||
| 1.2 Description of TNFSF proteins | 2 | ||
| 1.2.1. TNFSF ligands | 2 | ||
| 1.2.2. TNF receptors superfamily | 5 | ||
| 1.2.3. Ligand-receptor binding models | 5 | ||
| 1.2.4. The lymphotoxin and tumor necrosis factor network | 6 | ||
| 1.3. Signaling pathways | 8 | ||
| 1.3.1. The TNF-TNFR pathway | 8 | ||
| 1.3.2. LTbR signaling and the alternative NF-kB pathway | 10 | ||
| 2. TNFSF and inflammation | 11 | ||
| 2.1. Acute inflammation | 11 | ||
| 2.2. Chronic inflammation and autoimmunity | 15 | ||
| 2.3. TNFSF signatures in human pathologies | 18 | ||
| 2.3.1. Rheumatoid arthritis | 18 | ||
| 2.3.2. Inflammatory bowel disease | 19 | ||
| 2.4. Experimental models and the TNFSF as drug targets | 21 | ||
| 3. Targeting TNFSF in the clinic | 26 | ||
| 3.1. TNF inhibitors | 26 | ||
| 3.2. Other TNFSF targets | 29 | ||
| 4. Summary | 31 | ||
| Acknowledgements | 32 | ||
| References | 32 | ||
| Chapter 2 Complement as a Mediator of Inflammation | 51 | ||
| 1. Introduction to the complement system | 51 | ||
| 1.1. What is complement? | 51 | ||
| 1.2. Initiation of complement activation | 52 | ||
| 1.3. Amplification in the activation pathways | 52 | ||
| 1.4. The amplification loop of the alternative pathway | 54 | ||
| 1.5. Amplification at the stage of C5 cleavage | 54 | ||
| 1.6. Assembly of the membrane attack complex | 55 | ||
| 1.7. Active products of complement activation | 55 | ||
| 1.8. Complement regulation | 57 | ||
| 1.9. Complement receptors | 57 | ||
| 2. Complement roles in health | 58 | ||
| 2.1. Protection against infection | 58 | ||
| 2.2. Immune complex solubilisation | 58 | ||
| 2.3. Priming adaptive immunity | 59 | ||
| 2.4. Regulating lipid metabolism | 59 | ||
| 3. Complement roles in disease | 60 | ||
| 3.1. Complement and autoimmunity | 60 | ||
| 3.2. Complement deficiencies | 61 | ||
| 3.3. Complement mutations and polymorphisms | 63 | ||
| 4. Complement as a driver of inflammation | 64 | ||
| 4.1. General principles | 64 | ||
| 4.2. Complement anaphylatoxins | 65 | ||
| 4.3. Membrane attack complex | 68 | ||
| 4.4. Complement and inflammasome activation | 70 | ||
| 5. Complement inhibitors as anti-inflammatory drugs | 71 | ||
| 5.1. Pathway blockers as anti-inflammatory drugs | 71 | ||
| 5.2. Blocking C3a and C5a to inhibit inflammation | 72 | ||
| 6. Summary and future prospects | 73 | ||
| References | 74 | ||
| Chapter 3 Lipids and Inflammation | 79 | ||
| 1. Introduction | 79 | ||
| 2. Lipids and inflammation in obesity | 80 | ||
| 3. Circulating plasma lipids and inflammation | 82 | ||
| 4. Specific lipid classes in inflammation | 84 | ||
| 4.1. Eicosanoids and related lipids | 84 | ||
| 4.1.1. COX enzymes, products, and their receptors | 84 | ||
| 4.1.2. Inhibition of COXs | 87 | ||
| 4.1.3. COX metabolites in inflammation | 87 | ||
| 4.1.4. LOX enzymes, products, and their receptors | 89 | ||
| 4.1.5. LOX metabolites in inflammation | 91 | ||
| 4.1.6. Transcellular generation of eicosanoids | 92 | ||
| 4.1.7. Endocannabinoids and inflammation | 94 | ||
| 4.1.8. Isoprostanes and inflammation | 96 | ||
| 4.2. Phospholipids in inflammation | 96 | ||
| 4.2.1. Aminophospholipid translocation in inflammation | 97 | ||
| 4.2.2. Oxidized phospholipids in inflammation | 97 | ||
| 4.2.3. Lysophospholipids (LP) and phosphatidic acid (PA) | 100 | ||
| 4.2.4. Phosphoinositides | 101 | ||
| 4.3. Ceramides/sphingolipids | 103 | ||
| 5. Lipid receptors in inflammation: PPAR and LXR | 105 | ||
| 5.1. Peroxisome proliferator-activated receptors (PPAR) | 105 | ||
| 5.2. Liver X receptor (LXR) | 107 | ||
| 6. Lipidomics of inflammation: Analysis of bioactive lipids | 107 | ||
| 7. Summary | 109 | ||
| References | 109 | ||
| Chapter 4 Reactive Oxygen Species | 125 | ||
| 1. Introduction | 125 | ||
| 2. Reactive oxygen species | 126 | ||
| 2.1. Superoxide | 127 | ||
| 2.2. Hydrogen peroxide | 128 | ||
| 2.3. Hydroxyl radical | 129 | ||
| 2.4. Hypochlorous acid | 129 | ||
| 2.5. Oxidative protein modification | 130 | ||
| 3. Oxidant–antioxidant balance | 131 | ||
| 4. ROS sources | 135 | ||
| 4.1. H2O2 as secondary enzymatic product | 135 | ||
| 4.2. Prokaryotic H2O2 | 136 | ||
| 4.3. O2 as secondary enzymatic product — Mitochondrial electron transport chain | 137 | ||
| 4.4. O2 and H2O2 as primary enzymatic product — NADPH oxidases | 139 | ||
| 4.4.1. NOX/DUOX structural organization | 140 | ||
| 4.4.2. NOX2 assembly and activation | 143 | ||
| 4.4.3. Regulation of other NOX/DUOX family members | 146 | ||
| 4.4.4. ROS deficiency due to NADPH oxidase variants including CGD | 147 | ||
| 5. ROS in immunity and inflammation | 148 | ||
| 5.1. Mitochondrial ROS in immunity and inflammation | 148 | ||
| 5.2. NOX2-derived ROS in immunity and inflammation | 150 | ||
| 6. Outlook | 152 | ||
| Acknowledgments | 153 | ||
| Glossary of acronyms and abbreviations | 153 | ||
| References | 155 | ||
| Chapter 5 Leukocyte Adhesion | 171 | ||
| 1. Leukocyte adhesion molecules | 172 | ||
| 1.1. Integrins | 172 | ||
| 1.1.1. Endothelial ligands for integrins | 180 | ||
| 1.1.2. ECM ligands for integrins | 181 | ||
| 1.2. Selectins | 181 | ||
| 1.3. Leukocyte ligands for selectins | 182 | ||
| 1.4. Immunoglobulin adhesion molecules | 183 | ||
| 2. Biomechanics of leukocytes adhesion under flow | 184 | ||
| 3. Adhesion cascade | 186 | ||
| 3.1. Deviations from the adhesion cascade | 187 | ||
| 4. Leukocyte subsets | 188 | ||
| 5. Leukocyte adhesion in lymphatics | 190 | ||
| 6. Leukocyte adhesion to thrombi | 190 | ||
| 7. Defects in leukocyte adhesion | 191 | ||
| References | 192 | ||
| Chapter 6 Neutrophil Extracellular Traps | 205 | ||
| 1. Introduction | 205 | ||
| 1.1. Introduction of neutrophils | 206 | ||
| 1.2. Discovery of NETs | 207 | ||
| 2. Architecture and composition of NETs | 208 | ||
| 3. Formation of NETs | 211 | ||
| 3.1. Suicidal NETosis | 211 | ||
| 3.2. Vital NETosis | 216 | ||
| 4. Induction of NETosis | 217 | ||
| 5. Regulation of NETosis | 219 | ||
| 5.1. Reactive oxygen species | 219 | ||
| 5.2. Neutrophil elastase | 220 | ||
| 5.3. Peptidylarginine deminase 4 | 220 | ||
| 6. Clearance of NETs | 221 | ||
| 7. General Functions of NETs | 222 | ||
| 8. Functions of NETs in disease | 223 | ||
| 9. Antimicrobial NETs | 224 | ||
| 9.1. Viral infections | 228 | ||
| 9.2. Bacterial infections | 229 | ||
| 9.3. Fungal infections | 234 | ||
| 9.4. Parasitic infections | 239 | ||
| 10. Cytotoxic NETs | 241 | ||
| 10.1. Cytotoxic activity of NETs | 242 | ||
| 10.2. Infection | 243 | ||
| 10.3. Sterile inflammation | 244 | ||
| 11. Prothrombotic NETs | 246 | ||
| 11.1. Endothelium | 247 | ||
| 11.2. Platelets | 248 | ||
| 11.3. Red blood cells | 248 | ||
| 11.4. Coagulation | 249 | ||
| 11.5. Thrombolysis | 249 | ||
| 11.6. Animal models of thrombosis | 250 | ||
| 11.7. Patients with thrombosis | 251 | ||
| 12. Immunogenic NETs | 251 | ||
| 12.1. NETs in systemic lupus erythematosus and vasculitis | 253 | ||
| 12.2. NETs in rheumatoid arthritis | 256 | ||
| 12.3. NETs in other autoimmune diseases | 256 | ||
| 13. Anti-inflammatory NETs | 257 | ||
| 14. Conclusions | 258 | ||
| Acknowledgments | 259 | ||
| References | 259 | ||
| Chapter 7 Sepsis | 277 | ||
| 1. Introduction | 277 | ||
| 1.1. Epidemiology of sepsis | 277 | ||
| 1.2. History of experimental and clinical sepsis studies | 278 | ||
| 2. Brief overview of pathophysiology | 278 | ||
| 2.1. Hyperinflammation | 278 | ||
| 2.2. Immunosuppression | 279 | ||
| 2.3. Long-term defects associated with sepsis | 280 | ||
| 3. Cellular and molecular consequences of sepsis | 280 | ||
| 3.1. Redox imbalance | 280 | ||
| 3.2. Defective Ca2+ homeostasis | 281 | ||
| 3.3. PARP1, PARP2 activation | 281 | ||
| 3.4. Mitochondrial dysfunction | 282 | ||
| 3.5. Apoptosis of lymphoid cells and immunosuppression | 282 | ||
| 3.6. Extracellular histones | 283 | ||
| 4. Role of complement in sepsis | 283 | ||
| 4.1. Complement activation in sepsis | 283 | ||
| 4.2. Role of C5a and its receptors in experimental sepsis | 284 | ||
| 4.3. Role of complement and extracellular histones in sepsis | 285 | ||
| 5. Current concepts, problems, and controversies in animal sepsis models | 286 | ||
| 5.1. Heterogeneity of animal models of sepsis | 287 | ||
| 5.2. Endotoxemia studies | 289 | ||
| 5.3. Use of rodents versus larger animals | 289 | ||
| 6. Current concepts, problems and controversies in human sepsis studies | 290 | ||
| 6.1. Concerns about current clinical classifications of human sepsis | 290 | ||
| 6.2. Failure in clinical trials, including recent clinical trials using antagonists of toll-like receptors | 290 | ||
| 6.3. Concerns about clinical trial endpoints | 292 | ||
| 6.4. The influence of age and co-morbidities\rin human sepsis | 292 | ||
| 6.5. Genomic analysis of septic humans | 293 | ||
| 6.6. Human sepsis biomarkers | 293 | ||
| 7. The current outlook on treatment of sepsis | 294 | ||
| References | 295 | ||
| Chapter 8 Granulomatous Inflammation | 303 | ||
| 1. Introduction | 303 | ||
| 1.1. Architecture of the granuloma | 305 | ||
| 1.2. Basic principles of the granulomatous inflammation | 306 | ||
| 2. Granulomatous inflammation of infectious origin | 309 | ||
| 2.1. Bacterial triggers | 309 | ||
| 2.1.1. Tuberculosis | 309 | ||
| 2.1.2. Leprosy | 312 | ||
| 2.2. Other bacterial triggers | 313 | ||
| 2.3. Fungal triggers | 313 | ||
| 2.3.1. Histoplasmosis | 313 | ||
| 2.3.2. Other fungal pathogens | 314 | ||
| 2.4. Viral triggers | 314 | ||
| 2.4.1. Hepatitis viruses | 314 | ||
| 2.4.2. Other viruses that can cause granulomatous inflammation | 315 | ||
| 2.5. Other infectious triggers | 315 | ||
| 2.5.1. Schistosomiasis | 315 | ||
| 2.5.2. Leishmaniasis | 318 | ||
| 3. Immune-related, idiopathic granulomatous inflammation | 319 | ||
| 3.1. Vasculitis | 319 | ||
| 3.1.1. Small-vessel vasculitis | 319 | ||
| 3.1.2. Large-vessel vasculitis | 322 | ||
| 3.1.2.1. Giant cell arteritis | 322 | ||
| 3.1.2.2. Takayasu’s arteritis | 325 | ||
| 3.2. Sarcoidosis | 326 | ||
| 3.3. Crohn’s disease | 327 | ||
| 3.4. Primary biliary cirrhosis | 329 | ||
| 3.5. Common variable immune deficiency | 330 | ||
| 4. Granulomatous inflammation associated with environmental and iatrogenic triggers | 331 | ||
| 4.1. Berylliosis | 331 | ||
| 4.2. Silicosis | 332 | ||
| 4.3. Foreign bodies and topical medication | 333 | ||
| 4.4. Other triggers | 334 | ||
| 4.4.1. Chronic granulomatous disease | 334 | ||
| 4.4.2. Granuloma annulare | 335 | ||
| 5. Conclusions | 336 | ||
| References | 336 | ||
| Index | 357 |