Mediators of Inflammation

Lewis Thomas has suggested that "Perhaps the inflammatory reaction should be regarded as a defense of an individual against all the rest of nature, symbolizing his individuality and announcing his existence as an entity. " Provision of these symbols and announcements is the task of various mediators of inflammation and this volume has been designed to present our current understanding of their biochemistry, cellular origins, pharmacology, and role in pathology. Unlike other volumes of collected papers, this book did not result from a specific conference or symposium at which each contributor presented his own, narrowly framed research experience. Rather, each of the chapters represents, in the form of a general review, a summary of our knowledge of the mediators and the mecha­ nisms by which they are released to launch the inflammatory response. Much effort has been taken to insure that the often conflicting terminology in this field is defmed in detail: many synonyms (e. g. , of the properdin system or the alternate pathway of complement activation) have been repeatedly presented, in order to avoid confusion. Although each of the contributors is actively engaged in the field of inflammation, few text figures or tables of ongoing research have been included; the overall aim was to provide a volume readily accessible to workers in other areas as well as to the general reader.

1. The Mediators of Inflammation.- 2. Mechanisms Common to Several Mediator Systems.- 2.1. Cellular Release.- 2.2. Fluid-Phase Activation.- 2.3. Bypass Mechanisms.- 2.4. Extracellular Control Loops.- 2.5. Intracellular Controls.- 3. Centrality of Phagocytes.- 4. References.- 1 Mechanisms of Mediator Release from Inflammatory cells.- 1. Introduction.- 2. General Characteristics of Mediator Release from Cells.- 2.1. Mediators.- 2.2. Morphology of the Noncy to toxic Release Process.- 2.3. Stimuli for Noncytotoxic Release.- 2.4. Mechanisms of Noncytotoxic Release.- 2.5. Cytotoxic Reactions.- 2.6. Release In Vivo.- 3. Platelets.- 3.1. Platelet Mediators.- 3.2. Morphology of the Release Reaction.- 3.3. Stimuli Inducing the Noncy to toxic Platelet Release Reactions.- 3.4. Mechanisms of Noncytotoxic Release from Platelets.- 3.5. Cytotoxic Reactions of Platelets.- 3.6. In Vivo Release from Platelets,.- 4. Mast Cells.- 4.1. Mast Cell Mediators.- 4.2. Morphology of the Release from Mast Cells.- 4.3. Stimuli Inducing Release from Mast Cells.- 4.4. Mechanisms of Release from Mast Cells.- 4.5. Cytotoxic Reactions of Mast Cells.- 4.6. In Vivo Release from Mast Cells.- 5. Basophils.- 5.1. Basophil Mediators.- 5.2. Morphology of the Release.- 5.3. Stimuli Inducing Basophil Release.- 5.4. Mechanisms of Release from Basophils.- 6. Neutrophils.- 6.1. Neutrophil Mediators.- 6.2. Morphology of Release from Neutrophils.- 6.3. Stimuli Inducing Neutrophil Release.- 6.4. Mechanisms of Release from Neutrophils.- 6.5. Cytotoxic Reactions of Neutrophils.- 6.6. Release from Neutrophils In Vivo.- 7. Macrophages.- 8. Mediator Release as a Secretory Phenomenon.- 9. References.- 2 Lysosomal Hydrolases and Inflammatory Materials.- 1. Introduction.- 2. Polymorphonuclear Leukocyte Lysosomes.- 2.1. Types.- 2.2. Phagosomes, Secondary Lysosomes, pH.- 3. Polymorphonuclear Leukocytes, Lysosomes, and Inflammation.- 4. Lysosomal Enzymes as Inflammatory Mediators.- 4.1. Acid Proteases.- 4.2. Neutral Proteases.- 4.3. Human Leukocyte Elastase-like Esterase.- 4.4. Human Leukocyte Collagenase.- 4.5. Neutral Proteases and Human Disease.- 5. Nonenzymatic Inflammatory Mediators.- 5.1. Cationic Proteins.- 5.2. Histamine.- 5.3. Leukocyte Pyrogen.- 5.4. Leukocytic Endogenous Mediator.- 6. Leukocyte-Derived Substances and Inflammatory Mediator Systems.- 6.1. Complement and Mediators of Chemotaxis.- 6.2. Coagulation and Fibrinolytic Systems.- 6.3. Leukokinins.- 7. Antibacterial Substances.- 8. Conclusions.- 9. References.- 3 The Plasma Kinin-Forming System.- 1. Introduction.- 2. Biological Activities of Components and Their Inhibition.- 2.1. The Several forms of Hageman Factor; PF/dil.- 2.2. Plasminogen Activator.- 2.3. Plasmin.- 2.4. Kallikrein.- 2.5. Bradykinin.- 2.6. Inhibitors of Enzymes in the Kinin-Forming System.- 3. Preparation and Physicochemical Characterization of Components.- 3.1. Precursor and Active Hageman Factor.- 3.2. Hageman Factor Fragments.- 3.3. Plasminogen Proactivator and Activator.- 3.4. Plasminogen and Plasmin.- 3.5. Prekallikrein and Kallikrein.- 3.6. Kininogen.- 3.7. Kininases.- 4. Methods of Assay.- 4.1. Functional Assays.- 4.2. Immunological Methods for Measuring Certain Components of the Kinin-Forming System.- 5. Components of the Kinin System in White Blood Cells.- 5.1. Kinin-Forming Enzymes and Leukokinins.- 5.2. Kininases.- 6. Role of the Kinin-Forming System in Inflammation.- 6.1. Activation of Hageman Factor.- 6.2. Interaction with Other Plasma Systems.- 7. References.- 4 The Complement and Properdin Systems.- 1. Introduction.- 2. Nomenclature.- 3. Chemistry.- 3.1. Complement System.- 3.2. Properdin System.- 3.3. Control Proteins.- 4. Reaction Mechanisms.- 4.1. General Principles.- 4.2. Classic Complement Activation.- 4.3. The Properdin System: Activation and Amplification.- 4.4. The Terminal Sequence.- 4.5. Control Mechanisms.- 5. Biological Activities.- 5.1. Permeability Factors.- 5.2. Chemotactic Factors.- 5.3. Adherence Phenomena.- 5.4. Membrane Damage.- 6. References.- 5 Histamine and Serotonin.- 1. Histamine.- 1.1. Introduction.- 1.2. Chemical Properties.- 1.3. Assay Methods.- 1.4. Distribution.- 1.5. Metabolism.- 1.6. Pharmacological and Physiological Effects.- 1.7. Effect at a Cellular and a Molecular Level.- 1.8. Role in Inflammation.- 2. Serotonin.- 3. References.- 6 Prostaglandins.- 1. Introduction.- 2. Chemistry.- 3. Physiological Actions.- 3.1. Induction of Inflammation.- 3.2. Release During Inflammation.- 3.3. Effects of Anti-inflammatory Drugs.- 4. Prostaglandins as Possible Modulators of Inflammation.- 5. Summary.- 6. References.- 7 Slow Reacting Substances.- 1. Introduction.- 2. Slow Reacting Substance (SRS).- 3. Slow Reacting Substance of Anaphylaxis (SRS-A).- 3.1. Pharmacological Properties.- 3.2. Physicochemical Properties.- 3.3. In Vitro Production.- 3.4. In Vivo Production.- 4. Concluding Comments.- 5. References.