Prostaglandins, Leukotrienes, Lipoxins, and PAF

The field of eicosanoid metabolism and function continues to grow. Synthesis of the prostaglandins from essential fatty acids was first described by Bergstrom and Sarnuelsson in 1964. The thromboxanes were discovered in 1975, the prostacyclins, by Moncada and Vane, in 1976, and the leukotrienes by Samuelsson in 1979. A new class of biologically active arachidonic acid metabolites named lipoxins was announced by Bengt Samuelsson in May 1984. Since that time major advances have been made in the molecular biology of the eicosanoids including the cloning of prostaglandin synthases and 5, 12, and 15-lipoxygenases from several different species, including man. This volume, Prostaglandins, Leukotrienes, Lipoxins, and P AF: Their Mechanism of Action, Molecular Biology, and Clinical Applications contains most of the papers presented in the plenary sessions of the Xlth International Washington Spring Symposium on Health Sciences. The book is divided into six parts, each covering a different aspect of this rapidly expanding field, and contains a total of 42 chapters by an internationally recognized group of authors in each area. Part I contains 11 chapters and covers the molecular biology and enzymology of prostaglandins and leukotrienes. Chapter 1 by the Editor details new mechanisms for the antiinflammatory glucocorticoids involving translational control of the messenger RNA for prostaglandin synthase. Chapter 2 by Yamamoto describes the molecular evolution of two distinct mammalian 12-lipoxygenases.

Proceedings of the XIth International Washington Spring Symposium at the George Washington University, held in Washington, D.C., May 13-17, 1991

I - Molecular Biology and Enzymology of Prostaglandins and Leukotrienes.- 1. Translational Control of Prostaglandin Synthase by Growth Factors and Glucocorticoids.- 2. Two Types of Arachidonate 12-Lipoxygenase Demonstrated by Enzymological and Molecular Immunological and Molecular Biological Studies.- 3. A Model for the Transcriptional Regulation of a Mouse PGH Synthase Gene.- 4. Catalytic Properties and Reaction Mechanism of 5-Lipoxygenase.- 5. Cloning, Expression and Site-Directed Mutagenesis of the cDNA for Human Placental NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase.- 6. Regulation of Cyclooxygenase Gene Expression in Vascular Endothelial Cells.- 7. Structure-Function Studies and Physiological Roles of Eicosanoids Metabolized by Cytochrome P450 ?-Hydrolases.- 8. Multiple Cyclooxygenases: Cloning of a Mitogen Inducible Form.- 9. Amino Acids Essential to Catalysis by Prostaglandin Endoperoxide Synthase.- 10. Allene Oxide Biosynthesis and Metabolism.- 11. Lipoxygenase, Cyclooxygenase and Leukotriene A4 Hydrolase: Quantitative Polymerase Chain Reaction and Expression Studies.- II - Regulatory Mechanisms in Eicosanoid Release and Metabolism.- 12. Annexins and Signal Transduction.- 13. Structural and Functional Properties of Mammalian Group III Cytosolic Phospholipases A2.- 14. Regulation of Plasma Membrane Phospholipase A2 Activity by Phosphorylation/Dephosphorylation: Is Glucocorticoid Action Mediated by Induction of Protein Phosphatase?.- 15. Eicosanoid/Signal Transduction Interactions: Evidence of Two Induced Pathways of Phosphoinositide Biosynthesis by LTB4 in Cultured Human Epidermal Cells.- 16. Prostaglandyl-Inositol Cyclic-Phosphate, A New Second Messenger.- 17. Incorporation of Hydroxyeicosatetraenoic Acids into Phospholipid Signalling Pathways.- 18.The Purification of Two Intracellular Phospholipase A2's and the Effects of Phopholipase A2 Activating Protein and Mellitin on Their Activities.- 19. Differential Activation of Phospholipase A2 Activity and Prostacyclin Production in Rat Vascular Smooth Muscle Cells and Cardiomyocytes.- III - Cardiovascular Pulmonary Interactions of Prostaglandins, Prostacyclins and Leukotrienes.- 20. Thromboxane A2/Prostaglandin H2 Receptors: A Growing Family of Receptor Subtypes.- 21. The Regulation of Prostacyclin Secretion in Endothelial Cells.- 22. Metabolism of Arachidonic Acid by Purified Lung Epithelial Cells.- 23. Recovery of Human Tracheal Cell Epithelial Cell Cyclooxygenase Following Inactivation.- 24. Aortic Microsomal Prostacyclin Synthesis During Diet Induced Hypercholesterolemia.- 25. Activation of Protein Kinase C Regulates LTB4 Receptor on Guinea Pig Eosinophils.- IV - Recent Advance in Paf Metabolism and Function.- 26. Novel Neutrophil Agonists: Oxidatively-Fragmented Phosphatidylcholines.- 27. Specific Binding of Tritium-Labeled Platelet-Activating Factor to Human Mononuclear Leukocyte Membranes: A Third Putative Receptor of Platelet-Activating Factor.- 28. Tyrosine Kinase Phosphorylation in Human Neutrophil Activation by PAF and Other Agonists.- 29. Platelet-Activating Factor (PAF) Receptor in Brain and Signal Transduction in Neurons.- V - Immune Reactions, Cancer and Inflammatory Processes.- 30. Influence of PGE2 and LTB4 on CD8+ Thymocytes.- 31. Modulation of Cytokine Gene Expression by LTB4 and PAF: Transcriptional and Post-Transcriptional Regulation.- 32. Hepoxilin A3 Induces Vascular Permeability in the Skin.- 33. Lipoxygenase Metabolism in the Regulation of Hematopoiesis.- 34. Lipid Bodies: Structurally Distinct, Non-Membranous Intracellular Sites ofEicosanoid Formation.- 35. Tumor Prostaglandins and Estrogen Receptors: Prediction of Survival in Patients with Early Breast Cancer.- VI - Clinical and Pharmacological Applications of Eicosanoids.- 36. Lipid Mediators in Transplantation Reperfusion Injury, Acute Rejection and Accelerated Transplant Atherosclerosis.- 37. Pharmacological Profile, Pharmacokinetics and Biotransformation of the 5-Lipoxygenase Inhibitor FLM 5011.- 38. Prostaglandin H Synthase: Perturbation of the Tyrosyl Radical as a Probe of Anti-Cyclooxygenase Agents.- 39. Selective Incorporation of HETEs into Epidermal Phospholipids.- 40. Lipoxin Generation in Human Whole Blood: Monitoring by Electron-Capture NICI/GC/MS.- 41. Therapeutic Aspects of Leukotriene Antagonists and Inhibitors.- 42. Tolerance to Cardiac Grafts Following Intra-Graft Infusion of 16,16 Dimethyl PGE2.