<br>Contributors</br><br>Preface</br><br>Acknowledgments</br><br>Section One Development of Mast Cells and Basophils</br><br> Chapter 1 Regulation of Mast Cell and Basophil Development by Stem Cell Factor and Interleukin-3</br><br> Introduction</br><br> SCF, a Ligand for the c-kit Receptor</br><br> Multiple Effects of SCF in Mast Cell Biology</br><br> SCF can Regulate Mast Cell Function In Vitro and In Vivo</br><br> Interleukin-3</br><br> Using IL-3-/- Mice to Assess the Role of IL-3 in Mast Cell and Basophil Development</br><br> Summary</br><br> Acknowledgments</br><br> References</br><br> Chapter 2 Gain-of-function Mutations of c-kit in Human Diseases</br><br> Introduction</br><br> Loss-of-function Mutation of c-kit</br><br> Stomach Lesions of W/Wv and SI/SId Mice</br><br> Gain-of-function Mutation of c-kit in Mast Cell Neoplasms</br><br> Sporadic Gastrointestinal Stromal Turnouts</br><br> Familial GIST</br><br> Conclusion</br><br> References</br><br> Chapter 3 Modulation of Mast Cell Development from Embryonic Haematopoietic Progenitors by Eotaxin</br><br> Chemokines and Their Receptors Play Diverse Roles as Mediators of Inflammation</br><br> Chemokines Participate in Multiple Mast Cell and Basophil Functions</br><br> Chemokine Secretion by Mast Cells</br><br> Eotaxin</br><br> Results</br><br> Discussion</br><br> References</br><br> Chapter 4 Regulation and Dysregulation of Mast Cell Survival and Apoptosis</br><br> Introduction</br><br> Regulation of Mast Cell Survival and Apoptosis by Growth Factors</br><br> Regulation of Mast Cell Survival and Apoptosis by Death Receptors</br><br> Regulation of Mast Cell Survival and Apoptosis by Perforin, Nitric Oxide and Bacterial Toxins</br><br> Regulation of Mast Cell Survival and Apoptosis by Irradiation and Chemical Agents</br><br> Perspective: Apoptosis and Mast Cell Disease</br><br> References</br><br>Section Two Phenotypic and Ultrastructural Features of Mast Cells and Basophils</br><br> Chapter 5 Ultrastructural Features of Human Basophil and Mast Cell Secretory Function</br><br> Introduction</br><br> Mechanism(s) of Histamine and CLC-P Secretion from Human Basophils, of Histamine Secretion from Human Mast Cells In Vitro and of TNF-α and Chymase Secretion from Rat Peritoneal Cells</br><br> Histamine Secretion from Human Mast Cells In Vivo</br><br> Heparin Secretion from Human Mast Cells In Vitro</br><br> The Vesiculovacuolar Organelle, a New Endothelial Permeability Structure</br><br> Acknowledgments</br><br> References</br><br> Chapter 6 Human Dendritic Mast Cells</br><br> Introduction</br><br> The Morphology of Human Dendritic Mast Cells</br><br> Functional Aspects and Future Lines of Research</br><br> Concluding Remarks</br><br> References</br><br> Chapter 7 The Phenotypic Similarities and Differences between Human Basophils and Mast Cells</br><br> Introduction</br><br> Morphology</br><br> Membrane Receptors</br><br> Cytoplasmic Contents</br><br> Mast Cell Phenotypes in Tissues</br><br> The Involvement of Mast Cells and Basophils in Asthma and Drug Reactions</br><br> Acknowledgments</br><br> References</br><br> Chapter 8 Interactions between Nerves and Mast Cells in Amphibians</br><br> Introduction</br><br> Morphology of Frog Mast Cells</br><br> Frog Mast Cells and Peripheral Nervous System</br><br> Occurrence of Mast Cells in the Central and Peripheral Nervous Systems of Mammals</br><br> Concluding Remarks</br><br> References</br><br>Section Three Signal Transduction in Mast Cells and Basophils</br><br> Chapter 9 Sequential Protein Kinase Activation and the Regulation of Mast Cell Cytokine Production</br><br> Introduction</br><br> Signaling Through Mast Cell Surface Receptors</br><br> MAPK Family Members</br><br> Transcriptional Regulation of TNF-α Production</br><br> Stem Cell Factor Receptor (c-kit)</br><br> Differentiation Signaling and Function of Mast Cells Derived from Bone Marrow and Embryonic Stem Cells</br><br> Identification of a Critical Role for MEKK2 in JNK Activation and Cytokine Production</br><br> Summary</br><br> Acknowledgments </br><br> References</br><br> Chapter 10 FcεRI-mediated Induction of TNF-α Gene Expression in Mast Cell Lines</br><br> Introduction</br><br> Chromosomal Location and Gene Structure of TNF-α</br><br> Regulation of TNF-α Gene Expression in Non-mast Cell Lines</br><br> FcεRI-dependent Regulation of TNF-α Production</br><br> Concluding Remarks</br><br> References</br><br> Chapter 11 Regulation of Mast Cell Degranulation by SHIP</br><br> Introduction</br><br> Structure and Binding Partners of SHIP</br><br> Biological Properties of SHIP</br><br> Properties of the SHIP Knockout Mouse</br><br> The Role of SHIP in FcεRI-induced Degranulation of Mast Cells</br><br> The Role of SHIP in Steel Factor-induced Signaling in Mast Cells</br><br> The Role of SHIP in Thapsigargin-induced Signaling in Mast Cells</br><br> A Model of IgE-induced Degranulation</br><br> Major Questions Remaining</br><br> Summary and Conclusions</br><br> Acknowledgments</br><br> References</br><br>Section Four Regulation of Mast Cell and Basophil Signaling and Secretion</br><br> Chapter 12 Immunoreceptor Tyrosine-based Inhibition Motif-dependent Negative Regulation of Mast Cell Activation and Proliferation</br><br> Introduction</br><br> SIRP-α can Negatively Regulate FcεRI-dependent Mast Cell Activation</br><br> FcγRIIB can Negatively Regulate c-kit-dependent Mast Call Proliferation</br><br> Conclusion</br><br> Acknowledgments</br><br> References</br><br> Chapter 13 Perspectives on the Regulation of Secretion from Human Basophils and Mast Cells</br><br> Introduction</br><br> Regulation of FcεRI Expression</br><br> Desensitization</br><br> Modification of Basophil Function by IL-3</br><br> Summary</br><br> References</br><br> Chapter 14 Interactions between Secretory IgA and Human Basophils</br><br> Introduction </br><br> Structure and Metabolism of sIgA</br><br> Pathophysiology of sIgA</br><br> sIgA-mediated Basophil Activation</br><br> Receptors for sIgA</br><br> Clinical Relevance of sIgA-mediated Basophil Activation</br><br> Concluding Remarks</br><br> Acknowledgments</br><br> References</br><br> Chapter 15 Regulation of Mast Cell Secretion by Interferon-γ and Nitric Oxide</br><br> Introduction</br><br> Interferon and Mast Cells</br><br> Do Mast Cells Produce Interferon-γ?</br><br> Nitric Oxide and Nitric Oxide Synthases</br><br> Nitric Oxide Effects on Mast Cells</br><br> Do Mast Cells Produce Nitric Oxide?</br><br> How does Nitric Oxide Regulate Mast Cells?</br><br> Nitric Oxide and Mast Cells In Vivo - Clinical Implications</br><br> Conclusion: Mast Cells, Interferon-γ and Nitric Oxide in Cell Interactions and Disease</br><br> Acknowledgments</br><br> References</br><br>Section Five Structure and Function of Mast Cell Proteases</br><br> Chapter 16 Human and Mouse Mast Cell Tryptases</br><br> Introduction</br><br> Identification and Cloning of Human Tryptase Genes</br><br> Identification and Cloning of Mouse Tryptase Genes</br><br> Biochemical Features of Human and Mouse Tryptases</br><br> Expression of Mouse and Human Tryptases in Cells and Tissues</br><br> Function of Human and Mouse Tryptases</br><br> Tryptase Metabolism</br><br> Concluding Remarks</br><br> References</br><br> Chapter 17 Expression, Function and Regulation of Mast Cell Granule Chymases during Mucosal Allergic Responses</br><br> Introduction</br><br> Investigating the Response of mMCP-1-/- Mice to Gastrointestinal Nematodes</br><br> Regulation of the Expression of mMCP-1 in mBMMC</br><br> Discussion</br><br> Acknowledgments</br><br> References</br><br> Chapter 18 Structure and Function of Human Chymase</br><br> Introduction</br><br> General Properties</br><br> X-ray Crystal Structure of rHC</br><br> The Extended Substrate-binding Site of Human Chymase</br><br> Modeling of the Human Chymase-angiotensin I Interaction</br><br> Summary</br><br> Acknowledgments</br><br> References</br><br> Chapter 19 Structure and Function of Human Mast Cell Tryptase</br><br> Introduction</br><br> Distribution and Secretion in Disease</br><br> Structure and Physicochemical Properties</br><br> Non-human Tryptases</br><br> Regulation of Tryptase Activity</br><br> Peptide Substrates</br><br> Protein Substrates</br><br> Actions on Cells and Tissues</br><br> Cellular Receptors for Tryptase</br><br> Tryptase as a Therapeutic Target</br><br> Acknowledgments</br><br> References</br><br>Section Six Nerve-Mast Cell Interactions: Physiology and Pathology</br><br> Chapter 20 Mast Cell-Nerve Interactions: Possible Significance of Nerve Growth Factor</br><br> Evidence for Mast Cell-Nerve Interactions</br><br> Possible Role of NGF</br><br> Acknowledgment</br><br> References</br><br> Chapter 21 Nerve Growth Factor, Mast Cells and Allergic Inflammation</br><br> Nerve Growth Factor: Early Discovery and Emerging Data</br><br> NGF and the Nervous System</br><br> NGF and the Endocrine System</br><br> NGF and the Immune System</br><br> NGF and Mast Cells</br><br> NGF and Inflammation</br><br> NGF and Allergic Responses</br><br> Behavioral Influence on NGF Levels and Allergic Responses</br><br> Possible Future Directions</br><br> Acknowledgments</br><br> References</br><br> Chapter 22 Interactions between Neurotrophins and Mast Cells</br><br> Definition and Basic Aspects of Neurotrophins</br><br> Mast Cells as a Source of Neurotrophic Factors</br><br> Effects of Neurotrophins on Mast Cells</br><br> Evidence that NGF is also a Human Mast Cell Growth Factor</br><br> Neurotrophin Receptors on Mast Cells</br><br> Clinical Findings Suggesting Mast Cell and Neurotrophin Activity</br><br> Mast Cells and Neurotrophins: Open Issues</br><br> Acknowledgment</br><br> References</br><br> Chapter 23 Modulation of Peripheral Neurotransmission Associated with Mast Cell Activation</br><br> Sensory (Afferent) Nervous System</br><br> Enteric Nervous System</br><br> Sympathetic Nervous System</br><br> Parasympathetic Nervous System</br><br> Summary</br><br> References</br><br> Chapter 24 Regulation of Gastrointestinal Mucin Production by Nerve-Mast Cell Interactions</br><br> Introduction</br><br> Neuronal Mediation of Mucin Secretion</br><br> Effects of Stress on Colonic Mucin and Prostaglandin Release</br><br> Role of Corticotropin-releasing Factor in Stress-induced Colonic Mucin Secretion</br><br> Neurotensin is an Important Mediator of Colonic Stress Responses</br><br> Mast Cells as a Major Link of Stress-mediated Mucin Secretion</br><br> CRF and NT as Mediators of Intestinal Mast Cell Activation During Stress</br><br> Clinical Implications</br><br> References </br><br>Section Seven Mast Cells and Basophils in Homeostasis and Host Defense</br><br> Chapter 25 Mast Cell-Enterobacteria Interactions during Infection</br><br> Introduction</br><br> Protective Role of Mast Cells Against Bacterial Infection</br><br> Mast Cell Phagocytosis of Bacteria</br><br> Molecular Basis for Mast Cell-Enterobacteria Recognition</br><br> Mast Cell Activation Via CD48</br><br> Interactions of Human Mast Cells with Enterobacteria</br><br> Final Thoughts</br><br> Acknowledgments</br><br> References</br><br> Chapter 26 Human Mast Cells and Basophils in Immune Responses to Infectious Agents</br><br> Introduction</br><br> Mast Cells in Host Defense Against Bacterial Infections</br><br> Mast Cells and Basophils in Helicobacterpylori Infection</br><br> Leukotrienes in the Defence against Bacterial and Viral Infections</br><br> Activation of Human Basophils and Mast Cells by Protein A</br><br> Activation of Human Basophils and Mast Cells by Protein L</br><br> Activation of Human Basophils by Pepstatin A</br><br> Endogenous Superallergen Protein Fv in Viral Hepatitis</br><br> Activation of Human Basophils and Mast Cells by HIV- 1 Glycoprotein gp120</br><br> The 'Three Faces' of Mast Cells and Basophils in the Immune Response to Infectious Agents</br><br> Acknowledgments</br><br> References</br><br> Chapter 27 Differential Regulation of Mast Cell Mediator Secretion by Bacterial Products</br><br> Introduction</br><br> Receptors for Bacteria on Mast Cells</br><br> Selective Mast Cell Responses to Specific Bacterial Products</br><br> Combined Signals Alter and Enhance Mast Cell Responses</br><br> Bacteria- and Bacterial Product-mediated Signaling Events in Mast Cells</br><br> Conclusions</br><br> References</br><br> Chapter 28 The Role of Mast Cells, Basophils and Interleukin-3 (IL-3) in Immune Responses to Parasites: Studies with Mast Cell- and IL-3-Deficient Mice</br><br> Studies of Parasite Infection in Genetically Mast Cell-deficient Mice</br><br> Assessing the Role of IL-3 in Host Responses to Nematodes using IL-3-/-Mice</br><br> KitW/KitW-v, IL-3-/-Mice Exhibit a Profound Impairment of Basophilia, Mucosal Mast Cell Development and Immunity During Infection with Strongyloides venezuelensis</br><br> Summary</br><br> Acknowledgments</br><br> References</br><br>Section Eight Mast Cells in Atherosclerosis and Cardiac Diseases</br><br> Chapter 29 Human Heart Mast Cells: Immunological Characterization In Situ and In Vitro</br><br> Introduction</br><br> Isolation of HHMC and Their Characterization In Situ</br><br> Histamine, Proteolytic Enzymes and Proteoglycans Synthesized by HHMC</br><br> Prostaglandins and Cysteinyl Leukotrienes Synthesized De Novo by HMMC</br><br> Immunological and Non-immunological Stimuli that Activate HHMC In Vitro</br><br> Mast Cells and Regulation of Coagulation and Fibrinogenolysis</br><br> HHMC in Systemic and Cardiac Anaphylaxis and in Anaphylactoid Reactions</br><br> HHMC and Atherosclerosis</br><br> HHMC in Patients with Myocarditis and Hyper-eosinophilia</br><br> HHMC and Angiogenesis in the Heart</br><br> HHMC and Myocardial Ischaemia</br><br> HHMC in Idiopathic and Ischaemic Cardiomyopathy</br><br> Perspective and Conclusions</br><br> Acknowledgments</br><br> References</br><br> Chapter 30 Mast Cells in Atherosclerotic Human Coronary Arteries: Implications for Coronary Fatty Streak Formation, Plaque Ulceration and Control of Local Haemostatic Balance</br><br> Introduction</br><br> Atherosclerosis is a Disorder of Lipid Metabolism in the Arterial Intima with a Strong Inflammatory Component</br><br> Circulating Mast Cell Progenitors also find Their way in to the Arterial Intima</br><br> Immunohistochemical Observations on Mast Cells in the Human Coronary</br><br> Arterial Intima</br><br> Potential Mechanisms by Which Mast Cells may Play a Role in Atherogenesis</br><br> Conclusion and Future Directions</br><br> Acknowledgments</br><br> References</br><br> Chapter 31 Role of Mast Cells in Endogenous Fibrinolysis and Related (Patho)physiological Processes</br><br> Introduction</br><br> Contribution of Mast Cells to Fibrinogen Extravasation and Fibrin Formation</br><br> Mast Cell-dependent Fibrinolysis: Role of Tryptase and Chymase</br><br> The Mast Cell as Site of tPA Expression</br><br> Human Mast Cells Express the Urokinase Receptor (uPAR, CD87)</br><br> Functional Significance of MC-tPA: Mast Cells are 'Pro-fibrinolytic' Cells</br><br> Molecular Basis of Mast Cell Dependent Fibrinolysis: Role of Inhibitors (PAIs)</br><br> Fibrin-independent Plasminogen Activation</br><br> Clinical Significance</br><br> Mast Cells Accumulate at the Site of Thrombosis</br><br> SCF Regulates Expression and Release of tPA in Mast Cells</br><br> Concluding Remarks and Future Directions</br><br> Acknowledgment</br><br> References</br><br> Chapter 32 Mast Cells in Myocardial Ischaemia and Reperfusion</br><br> Introduction</br><br> Mast Cells in Normal Hearts</br><br> The Mast Cell as a Source of Cytokines</br><br> Mast Cell Degranulation Following Myocardial Ischaemia</br><br> Mast Cells in Healing Myocardial Infarcts</br><br> Mast Cell Precursors Infiltrate the Healing Heart</br><br> SCF Induction Following Myocardial Ischaemia/Reperfusion</br><br> Macrophages are the Main Source of SCF Following Myocardial Ischaemia</br><br> Potential Role of Mast Cells in Healing</br><br> The Mast Cell in Myocardial Ischaemia/Reperfusion: Friend or Foe?</br><br> Acknowledgment</br><br> References</br><br>Section Nine Leukotrienes, Cytokines and Chemokines in Allergic Disorders</br><br> Chapter 33 Lipid Mediators from Mast Cells and Basophils in Allergic Diseases</br><br> Introduction</br><br> Arachidonic Acid Pools in Human Mast Cells and Basophils</br><br> Phospholipase A 2 in Human Mast Cells and Basophils</br><br> Extracellular Effects of Mast Cell-derived Secretory PLA 2</br><br> PAF and Related Phospholipids</br><br> Concluding Remarks</br><br> Acknowledgments</br><br> References</br><br> Chapter 34 Regulation and Function of Human Intestinal Mast Cells</br><br> Introduction</br><br> Effector Functions of Human Intestinal Mast Cells</br><br> Regulation of Human Intestinal Mast Cell Functions</br><br> Clinical Implications</br><br> Future Directions</br><br> References</br><br> Chapter 35 Differential Regulation of Basophil Functions by Chemokines</br><br> Basophil Phenotype and Functions</br><br> Chemokines</br><br> Acknowledgment</br><br> References</br><br> Chapter 36 Chemokine Receptors on Human Mast Cells</br><br> Chemokines</br><br> Mast Cells</br><br> Chemokine Receptors on MC</br><br> Concluding Remarks</br><br> Acknowledgment</br><br> References</br><br> Chapter 37 Release and Cleavage of Stem Cell Factor by Human Mast Cells</br><br> Introduction</br><br> Stem Cell Factor Expression in Human Mast Cells</br><br> Stem Cell Factor-Protease Interactions</br><br> Biological Effects of SCF1-166 and SCF1-159 Oil HLMC and HSMC</br><br> Conclusions</br><br> Acknowledgments</br><br> References</br><br> Chapter 38 SCF-Induced Chemokine Production, Allergic Airway Inflammation and Airway Hyper-reactivity</br><br> Introduction</br><br> SCF-Induced Mast Cell Activation, Inflammation and Airway Hyper-reactivity</br><br> Regulation of SCF Production</br><br> Initiation of Cytokine/Chemokine Production by SCF in Mast Cells and Eosinophils</br><br> Structural Cell-derived SCF Contributes to Disease Progression: Differential Activation of Mast Cells by Soluble versus Membrane SCF</br><br> Summary</br><br> References</br><br>Section Ten Clinical Implications of Histamine H1 Receptor Antagonists</br><br> Chapter 39 Pharmacological Profile of Mizolastine, a Novel Histamine H1 Receptor Antagonist</br><br> Histamine and Its Receptor Subtypes</br><br> Specificity and Selectivity of Mizolastine for H1 Histamine Receptor Subtypes</br><br> Antihistaminergic Effects of Mizolastine</br><br> Allergic Reaction</br><br> Anti-anaphylactic Properties of Mizolastine</br><br> Immune System-mediated Inflammatory Reaction in Allergy</br><br> Anti-allergic Effects of Mizolastine</br><br> Other Pharmacological Effects of Mizolastine</br><br> Conclusion</br><br> Acknowledgment</br><br> References</br><br> Chapter 40 Adenosine-Induced Enhancement of Mast Cell Mediator Release in Asthma and COPD</br><br> Introduction</br><br> The Bronchoconstrictor Effect of Adenosine in Asthma</br><br> The Airway Response to Adenosine in COPD</br><br> Adenosine Receptors on Mast Cells</br><br> Concluding Comments</br><br> References</br><br> Chapter 41 Neural Activation and Inflammation in Allergic Rhinitis</br><br> Introduction</br><br> Neurogenic Inflammation</br><br> Neural Hyper-responsiveness</br><br> Nerve Growth Factor</br><br> Summary and Conclusion</br><br> References</br><br> Chapter 42 Antihistaminic and Anti-inflammatory Effects of Mizolastine</br><br> Introduction</br><br> Pharmacokinetics of Mizolastine</br><br> Clinical Efficacy of Mizolastine</br><br> Anti-inflammatory effects of Mizolastine</br><br> Concluding Remarks</br><br> References</br><br> Chapter 43 Electrophysiological and Molecular Basis for the Adverse Cardiovascular Effects of Histamine H, Receptor Antagonists</br><br> Introduction</br><br> Cardiotoxicity of Second-generation Antihistamines</br><br> Conclusions</br><br> Acknowledgments</br><br> References</br><br>Index</br><br></br>