This volume forms part of a prestigious series and covers the latest advances in our understanding of the pathophysiology and treatment of asthma. Our understanding of asthma has changed dramatically in recent years, and much of this new information is brought together in this volume written by inter nationally recognised authorities. The aim of the book is to review in depth the changing concepts of inflammatory processes in asthma and to discuss the implications for research of this common chronic disease. Many of the advances in and future therapy our understanding of asthma have originated from a pharmacological approach, and this volume highlights the promising new options for pharma cological intervention. It is hoped this book will be invaluable for research scientists and clinic ians involved in asthma research and will be a major reference resource for chest physicians and those involved in the development of novel pharmaceu tical entities. Each chapter is extensively referenced, generously illustrated with clear diagrams and photographs, and represents a state-of-the-art review of this growing area. c.P. PAGE P.l. BARNES Contents CHAPTER 1 The Pathology of Asthma: An Overview L.A. LAmNEN and A. LAmNEN. With 10 Figures. 1 A. Introduction. 1. B. Methods to Investigate the Pathology of Human Asthma. 1 C. Bronchial Epithelium and Inflammatory Cells in Asthmatic Patients Between Attacks. 2 I. Mast Cells. 4. II. Eosinophils. 7 III. Neutrophils. 10 D. Bronchial Epithelial Inflammation During an Asthma Attack. 10 E. Epithelial Regeneration. 12.

Inhaltsangabe1 The Pathology of Asthma: An Overview.- A. Introduction.- B. Methods to Investigate the Pathology of Human Asthma.- C. Bronchial Epithelium and Inflammatory Cells in Asthmatic Patients Between Attacks.- I. Mast Cells.- II. Eosinophils.- III. Neutrophils.- D. Bronchial Epithelial Inflammation During an Asthma Attack.- E. Epithelial Regeneration.- F. Airway Smooth Muscle.- G. Bronchial Glands.- H. Neural Pathways.- I. Epithelium.- II. Neuroepithelial Bodies and Neuroendocrine-Like (Granule-Containing) Cells.- I. Nerves and Other Airway Structures.- J. Bronchial Circulation.- K. Leakage of the Bronchial Vascular Bed in Patients with Asthma.- L. Conclusion.- References.- 2 The Contribution of Inflammatory Cells to the Pathogenesis of Asthma.- A. Inflammation and Inflammatory Cells.- B. Pathological Evidence for Inflammation in Asthma.- C. Microvascular Leakage.- D. Neutrophils.- E. Eosinophils.- F. Mast Cells and Basophils.- G. Monocytes and Macrophages (Mononuclear Phagocytes).- H. Platelets.- I. Lymphocytes.- J. Concluding Comments.- References.- 3 Inflammatory Mediators.- A. Introduction.- I. Cellular Origin of Mediators.- II. Mediator Effects.- III. Mediator Receptors.- IV. Mediator Interactions.- V. Mediator Antagonists.- B. Histamine.- I. Synthesis and Metabolism.- II. Histamine Receptors.- III. Airway Effects.- IV. Role in Asthma.- C. Cyclooxygenase Products.- I. Synthesis and Metabolism.- II. Receptors.- III. Airway Effects.- 1. Airway Smooth Muscle.- 2. Secretion.- 3. Inflammatory Effects.- IV. Role in Asthma.- D. Lipoxygenase Products.- I. Synthesis and Metabolism.- II. Receptors.- III. Airway Effects.- 1. Airway Smooth Muscle.- 2. Secretion.- 3. Vascular Effects.- 4. Cellular Activation.- 5. Effects on Bronchial Responsiveness.- IV. Role in Asthma.- E. PAF.- I. Origin.- 1. Synthesis.- 2. Cellular Origin.- 3. Metabolism.- II. Receptors.- III. Airway Effects.- 1. Airway Smooth Muscle.- 2. Airway Secretions.- 3. Vascular Effects.- 4. Inflammatory Cell Activation.- 5. Bronchial Hyperresponsiveness.- IV. Role in Asthma.- 1. Release of PAF in Asthma.- 2. PAF Antagonists.- F. Kinins.- I. Formation and Metabolism.- II. Receptors.- III. Airway Effects.- IV. Role in Asthma.- G. Adenosine.- I. Origin.- II. Receptors.- III. Actions.- IV. Role in Asthma.- H. Complement.- I. Origin and Metabolism.- II. Receptors.- III. Airway Effects.- 1. Smooth Muscle Contraction.- 2. Vascular Effects.- 3. Mucus Secretion.- 4. Chemotaxis and Cell Activation.- 5. Bronchial Hyperresponsiveness:.- IV. Role in Asthma.- I. Serotonin.- I. Origin.- II. Receptors.- III. Airway Effects.- J. Chemotactic Factors.- K. Oxygen Radicals.- L. Conclusions.- References.- 4 Pharmacology of Airway Smooth Muscle.- A. Introduction.- B. E/C Coupling Mechanisms.- I. The Airway Smooth Muscle Cell.- II. Activator Calcium Ions and E/C Coupling.- 1. Coupling Mechanisms.- 2. Extracellular Activator Ca2+.- 3. Intracellular Activator Ca2+.- III. Biochemical Basis of Airway Smooth Muscle Contraction.- C. E/C Uncoupling Mechamisms.- I. ?-Adrenoceptor Agonists.- 1. ?-Agonist-Induced Relaxation In Vitro: General Properties.- 2. Role of Cyclic Adenosine Monophosphate (cAMP) Accumulation in the Relaxant Actions of ?-Adrenoceptor Agonists.- 3. ?-Agonists and the Ca2+ Sensitivity (or Responsiveness) of the Contractile Machinery.- 4. ?-Agonists and Inhibition of Ca2+ Influx.- 5. ?-Agonists and Inhibition of Ca2+ Release from Intracellular Stores.- 6. ?-Agonists and Promotion of Ca2+ Sequestration by Intracellular Stores.- 7. ?-Agonists and Ca2+ Extrusion.- II. Alkylxanthines.- 1. Alkylxanthine-Induced Relaxation In Vitro: General Properties.- 2. Role of cAMP Accumulation in the Relaxant Actions of Alkylxanthines.- 3. Alkyxanthines and Reduction in the Ca2+ Sensitivity (or Responsiveness) of the Contractile Machinery.- 4. Alkylxanthines and Inhibition of Ca2+ Influx.- 5. Alkylxanthines and Inhibition of Ca2+ Release from Intracellular Stores.- 6. Alkylxanthines and Promotion of Ca2+ Sequ