Platelet-Activating Factor and Related Lipid Mediators, Softcover reprint of the original 1st ed. 1987

Platelet-activating factor (PAF) is the commonly used name for a group of potent biologically active, ether-linked phospholipids, the alkylacetylglycerophospho­ cholines. Following the identification of the chemical structure of P AF in 1979, much progress has been made in our understanding of these phospholipid medi­ ators. This is particularly true from the points of view of their molecular structural requirements for expression of biological activity, their biosynthesis and cata­ bolism, their diverse range of biological activities, evidence for their specific recep­ tors at the cell surface, the development of specific antagonists for use in receptor studies and for testing as potential anti-PAF drugs, and implications about their involvement in health and disease. Chapters in this book cover the current status of these general areas of PAF research. Although an enormous amount of information has been published about this interesting new type of phospholipid mediators, questions about their mechanism of action, regulatory controls, and the precise role and relative importance of P AF in specific diseases and physiological functions remain to be answered. Since the 1979 discovery, the PAF field has brought together scientists from a variety of different biomedical disciplines. The diversity of scientists now in PAF research is very apparent from the number of P AF publications appearing in a wide array of scientific journals, ranging from molecular biology to clinical medicine. Publications related to PAF continue to increase at an amazingly rapid rate, with the pace reminiscent of the period following the discovery of prostaglandins.

Introduction: Historical Aspects of Alkyl Lipids and Their BiologicallyActive Forms (Ether Lipids,Platelet-Activating Factor, andAntihypertensive Renal Lipids).- I. Methodology and Chemistry.- 1. Chemical Synthesis and Mass Spectrometry of PAF.- 1. Introduction.- 2. Chemical Synthesis of PAF.- 3. Mass Spectrometry.- References.- 2. Chromatographic Analyses of Ether-Linked LipidsInvolved in PAF Metabolism.- 1. Introduction.- 2. Chromatographic Separations of PAF and Related Analogs.- 3. Analyses of PAF-Related Lipids.- 4. Summary.- References.- II. Composition.- 3. Composition of Alkyl Ether-Linked Phospholipids in Mammalian Tissues.- 1. Introduction.- 2. Contents of Alk-1-enylacyl, Alkylacy1, and Diacyl Phospholipids in Mammalian Tissues.- 3. Fatty Chain Composition and Molecular Species of  ther and Diacyl Phospholipids.- 4. Structure of Naturally Occurring PAF.- References.- III. Enzymes.- 4. Enzymatic Pathways for Platelet-Activating Factor, Related Alkyl Glycerolipids, their Precursors.- 1. Introduction.- 2. Precursors of Ether Lipids: Fatty Alcohols and Acyldihydroxyacetone-P.- 3. Formation of the Alkyl-Ether Bond in Lipids: Alkyldihydroxyacetone-P, the First Detectable Intermediate.- 4. Biosynthesis of l-Alkyl-2-lyso-sn-glycero-3-P, a Branchpoint in PAF Metabolism: Alkyldihydroxyacetone-P, Alkyldihydroxyacetone, or Alkylglycerols as Precursors.- 5. Biosynthesis of Alkylacetylglycerols, a Direct Precursor of PAF.- 6. Biosynthesis of PAF via the DTT-Insensitive Cholinephosphotransferase.- 7. Biosynthesis of Alkylacylglycerols.- 8. Conversion of Alkylacylglycerols to Alkylacylglycerophosphocholines, the Stored Precursor of PAF.- 9. Activation of PAF via the PAF Cycle: Role of Phospholipase A2 and Acetyltransferase with Lyso-PAF as the Intermediate.- 10. Inactivation of PAF via the PAF Cycle: Role of Acetylhydrolase and the Subsequent Conversion of Lyso-PAF to Alkylarachidonoylglycerophosphocholines via a Transacylase.- 11. Cleavage of the Alkyl-Ether Bond: Pte°H4-Dependent Alkylmonoxygenase.- 12. Lysophospholipase D.- 13. Phospholipase C.- 14. Summary.- References.- 5. Enzymatic Control of the Cellular Levels of Platelet-Activating Factor.- 1. Cell Types and Stimuli in the Production of PAF.- 2. Pool Sizes of PAF Precursors.- 3. Alkyllyso-GPC: Acetyl-CoA Acetyltransferase.- 4. Dithiothreitol-Insensitive Cholinephosphotransferase.- 5. Alkylacetyl-GPC Acetylhydrolase.- 6. Phospholipase A2.- 7. Conclusions.- References.- IV. Antagonists, Agonists, and Receptors.- 6. Platelet-Activating Factor Binding to Specific Cell Membrane Receptors.- 1. Introduction.- 2. Methods for Quantifying PAF Binding.- 3. PAF Binding to Intact Cells.- 4. Characteristics of PAF Binding to Platelets.- 5. PAF Binding to Membrane Preparations.- 6. Isolation of the PAF Receptor.- 7. PAF Receptor Antagonists.- 8. Mechanisms of Activating Signal Transduction.- 9. Specific Desensitization to PAF.- References.- 7. The Chemical and Biological Properties of PAF Agonists, Antagonists and Biosynthetic Inhibitors.- 1. Introduction.- 2. PAF Agonists.- 3. PAF Antagonists.- 4. Inhibitors of PAF Biosynthesis.- 5. Conclusions.- References.- 8. Conformational Properties of the PAF-Acether Receptor on Platelets Based on Structure—Activity Studies.- 1. Introduction.- 2. Presence and Characteristics of PAF-Acether Receptors.- 3. Structure-Activity Relations for PAF-Acether Agonists.- 4. Antagonists of PAF-Acether.- 5. Conformation of Specific Membrane PAF-Acether Binding Sites and Its Modification During Cell Activation.- References.- V. Biochemical and Biological Aspects in Specific Cells and Tissues.- 9. Diversity of the Biochemical and Biological Behavior of Platelet-Activating Factor.- 1. Introduction.- 2. Metabolic Alterations Initiated by Platelet-Activating Factor in Various Tissues and Organs.- 3. Summary.- References.- 10. Extracellular and Intracellular Activities of PAF.- 1. Introduction.- 2. Requirement for Cell Stimulation to Initiate PAF Synthesis.- 3. PAF as a Mediator.- 4. Harmful and Beneficial Aspects of Extracellular PAF Action: A Dualistic Problem.- 5. Intracellular PAF.- 6. Summary.- References.- 11. Interrelationships in the Metabolism of Platelet-Activating Factorand Arachidonate in Neutrophils.- 1. Metabolic Pathways of PAF in Neutrophils.- 2. Associations in the Metabolism of Archidonate and PAF in Neutrophils.- 3. Related Interactions of PAF and Arachidonate.- 4. Conclusions.- References.- 12. Platelet-Activating Factor: Mechanisms of Cellular Activation.- 1. Introduction.- 2. Actions of PAF and Structural Analogs.- 3. PAF Receptors.- 4. PAF Antagonists.- 5. PAF and GTP Proteins.- 6. PAF and Ca2+.- 7. PAF and Other Lipid Mediator Systems.- 8. Conclusions.- References.- 13. The Role of Platelet-Activating Factor in Inflammation.- 1. Introduction.- 2. Release of PAF in in Vitro Models of Hypersensitivity Reactions.- 3. Resease of PAF in Vivo in Various Types of Hypersensitivity Reactions.- 4. Tissue Injury Induced by Systemic or Local Administration of PAF in Laboratory Animals.- 5. Release of PAF Induced by Nonimmunological Stimuli.- 6. Conclusions.- References.- 14. The Production of Platelet-Activating Factor by Cultured Human Endothelial Cells: Regulation and Function.- 1. Introduction.- 2. Cultured Endothelial Cells Derived from Umbilical Vein Produce PAF.- 3. Regulation of PAF Production in Endothelial Cells.- 4. Interaction of PAF and Eicosanoid Metabolism in Endothelial Cells.- 5. Function of Endothelial-Associated PAF.- 6. Conclusions.- References.- 15. Bronchopulmonary Pharmacology of PAF-Acether.- 1. Introduction.- 2. Effects of PAF-Acether on the Bronchorespiratory System.- 3. Physiopathology of PAF-Acether with Respect to Pulmonary Functions.- References.- 16. Platelet-Activating Factor: A Secretory Product from Phagocytes.- 1. Introduction.- 2. In Vivo Studies.- 3. Pathophysiological Consequences of the Generation of PAF-Acether.- 4. Modulation of PAF-Acether Generation in PolymorphonuclearLeukocytes.- 5. Modulation of the Biosynthesis of PAF-Acether in Splenic Microsomes.- 6. Concluding Remarks.- References.- 17. Functions of PAF in Reproduction and Development: Involvement of PAF in Fetal Lung Maturation and Parturition.- 1. Introduction.- 2. Identification and Distribution of PAF in Human Amniotic Fluid.- 3. PAF Biosynthesis and Function During Fetal Lung Maturation.- 4. Role of PAF in the Initiation of Parturition.- References.- 18. Effect of PAF on the Cardiovascular System.- 1. Introduction.- 2. Systemic Effects of PAF.- 3. PAF-Induced Shock.- 4. Effect of PAF on Blood Vessels and the Microcirculation.- 5. Antihypertensive Polar Renomedullary Lipids (APRL).- 6. Cardiac and Coronary Effects of PAF.- 7. Summary.- References.- 19. Biosynthesis and Release of PAF-Acether by Mouse Bone Marrow-Derived Mast Cells.- 1. Introduction.- 2. Generation of PAF-Acether from Mast Cells.- 3. Biosynthesis of PAF-Acether by Mouse Bone Marrow-Derived Mast Cells.- 4. Concluding Remarks.- References.- VI. Antitumor Analogs of PAF.- 20. Antineoplastic Actions of Ether Lipids Related to Platelet-Activating Factor.- 1. Introduction..- 2. Activity of Alkyl-Lysophospholipid Derivatives and Other Ether Lipid Derivatives on Experimental Tumor Growth in Vivo.- 3. Activity of Alkyl-Lysophospholipid Derivatives and Other Ether Lipids on Experimental Metastasis in Vivo.- 4. Influence of Alkyl-Lysophospholipid Derivatives on Tumorigenesis.- 5. Mode of Action: Experimental Evidence and Hypothesis.- 6. Preclinical Screening of Various Ether Lipids and Derivatives for Antineoplastic Activity.- 7. Clinical Pilot Studies with ET-18-OCH3 as an Alkyl-Lysophospholipid of the First Generation.- 8. Conclusions and Future Aspects.- References.