Mast Cells and Basophils

Contributors

Preface

Acknowledgments

Section One Development of Mast Cells and Basophils

Chapter 1 Regulation of Mast Cell and Basophil Development by Stem Cell Factor and Interleukin-3

Introduction

SCF, a Ligand for the c-kit Receptor

Multiple Effects of SCF in Mast Cell Biology

SCF can Regulate Mast Cell Function In Vitro and In Vivo

Interleukin-3

Using IL-3-/- Mice to Assess the Role of IL-3 in Mast Cell and Basophil Development

Summary

Acknowledgments

References

Chapter 2 Gain-of-function Mutations of c-kit in Human Diseases

Introduction

Loss-of-function Mutation of c-kit

Stomach Lesions of W/Wv and SI/SId Mice

Gain-of-function Mutation of c-kit in Mast Cell Neoplasms

Sporadic Gastrointestinal Stromal Turnouts

Familial GIST

Conclusion

References

Chapter 3 Modulation of Mast Cell Development from Embryonic Haematopoietic Progenitors by Eotaxin

Chemokines and Their Receptors Play Diverse Roles as Mediators of Inflammation

Chemokines Participate in Multiple Mast Cell and Basophil Functions

Chemokine Secretion by Mast Cells

Eotaxin

Results

Discussion

References

Chapter 4 Regulation and Dysregulation of Mast Cell Survival and Apoptosis

Introduction

Regulation of Mast Cell Survival and Apoptosis by Growth Factors

Regulation of Mast Cell Survival and Apoptosis by Death Receptors

Regulation of Mast Cell Survival and Apoptosis by Perforin, Nitric Oxide and Bacterial Toxins

Regulation of Mast Cell Survival and Apoptosis by Irradiation and Chemical Agents

Perspective: Apoptosis and Mast Cell Disease

References

Section Two Phenotypic and Ultrastructural Features of Mast Cells and Basophils

Chapter 5 Ultrastructural Features of Human Basophil and Mast Cell Secretory Function

Introduction

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

Histamine Secretion from Human Mast Cells In Vivo

Heparin Secretion from Human Mast Cells In Vitro

The Vesiculovacuolar Organelle, a New Endothelial Permeability Structure

Acknowledgments

References

Chapter 6 Human Dendritic Mast Cells

Introduction

The Morphology of Human Dendritic Mast Cells

Functional Aspects and Future Lines of Research

Concluding Remarks

References

Chapter 7 The Phenotypic Similarities and Differences between Human Basophils and Mast Cells

Introduction

Morphology

Membrane Receptors

Cytoplasmic Contents

Mast Cell Phenotypes in Tissues

The Involvement of Mast Cells and Basophils in Asthma and Drug Reactions

Acknowledgments

References

Chapter 8 Interactions between Nerves and Mast Cells in Amphibians

Introduction

Morphology of Frog Mast Cells

Frog Mast Cells and Peripheral Nervous System

Occurrence of Mast Cells in the Central and Peripheral Nervous Systems of Mammals

Concluding Remarks

References

Section Three Signal Transduction in Mast Cells and Basophils

Chapter 9 Sequential Protein Kinase Activation and the Regulation of Mast Cell Cytokine Production

Introduction

Signaling Through Mast Cell Surface Receptors

MAPK Family Members

Transcriptional Regulation of TNF-α Production

Stem Cell Factor Receptor (c-kit)

Differentiation Signaling and Function of Mast Cells Derived from Bone Marrow and Embryonic Stem Cells

Identification of a Critical Role for MEKK2 in JNK Activation and Cytokine Production

Summary

Acknowledgments

References

Chapter 10 FcεRI-mediated Induction of TNF-α Gene Expression in Mast Cell Lines

Introduction

Chromosomal Location and Gene Structure of TNF-α

Regulation of TNF-α Gene Expression in Non-mast Cell Lines

FcεRI-dependent Regulation of TNF-α Production

Concluding Remarks

References

Chapter 11 Regulation of Mast Cell Degranulation by SHIP

Introduction

Structure and Binding Partners of SHIP

Biological Properties of SHIP

Properties of the SHIP Knockout Mouse

The Role of SHIP in FcεRI-induced Degranulation of Mast Cells

The Role of SHIP in Steel Factor-induced Signaling in Mast Cells

The Role of SHIP in Thapsigargin-induced Signaling in Mast Cells

A Model of IgE-induced Degranulation

Major Questions Remaining

Summary and Conclusions

Acknowledgments

References

Section Four Regulation of Mast Cell and Basophil Signaling and Secretion

Chapter 12 Immunoreceptor Tyrosine-based Inhibition Motif-dependent Negative Regulation of Mast Cell Activation and Proliferation

Introduction

SIRP-α can Negatively Regulate FcεRI-dependent Mast Cell Activation

FcγRIIB can Negatively Regulate c-kit-dependent Mast Call Proliferation

Conclusion

Acknowledgments

References

Chapter 13 Perspectives on the Regulation of Secretion from Human Basophils and Mast Cells

Introduction

Regulation of FcεRI Expression

Desensitization

Modification of Basophil Function by IL-3

Summary

References

Chapter 14 Interactions between Secretory IgA and Human Basophils

Introduction

Structure and Metabolism of sIgA

Pathophysiology of sIgA

sIgA-mediated Basophil Activation

Receptors for sIgA

Clinical Relevance of sIgA-mediated Basophil Activation

Concluding Remarks

Acknowledgments

References

Chapter 15 Regulation of Mast Cell Secretion by Interferon-γ and Nitric Oxide

Introduction

Interferon and Mast Cells

Do Mast Cells Produce Interferon-γ?

Nitric Oxide and Nitric Oxide Synthases

Nitric Oxide Effects on Mast Cells

Do Mast Cells Produce Nitric Oxide?

How does Nitric Oxide Regulate Mast Cells?

Nitric Oxide and Mast Cells In Vivo - Clinical Implications

Conclusion: Mast Cells, Interferon-γ and Nitric Oxide in Cell Interactions and Disease

Acknowledgments

References

Section Five Structure and Function of Mast Cell Proteases

Chapter 16 Human and Mouse Mast Cell Tryptases

Introduction

Identification and Cloning of Human Tryptase Genes

Identification and Cloning of Mouse Tryptase Genes

Biochemical Features of Human and Mouse Tryptases

Expression of Mouse and Human Tryptases in Cells and Tissues

Function of Human and Mouse Tryptases

Tryptase Metabolism

Concluding Remarks

References

Chapter 17 Expression, Function and Regulation of Mast Cell Granule Chymases during Mucosal Allergic Responses

Introduction

Investigating the Response of mMCP-1-/- Mice to Gastrointestinal Nematodes

Regulation of the Expression of mMCP-1 in mBMMC

Discussion

Acknowledgments

References

Chapter 18 Structure and Function of Human Chymase

Introduction

General Properties

X-ray Crystal Structure of rHC

The Extended Substrate-binding Site of Human Chymase

Modeling of the Human Chymase-angiotensin I Interaction

Summary

Acknowledgments

References

Chapter 19 Structure and Function of Human Mast Cell Tryptase

Introduction

Distribution and Secretion in Disease

Structure and Physicochemical Properties

Non-human Tryptases

Regulation of Tryptase Activity

Peptide Substrates

Protein Substrates

Actions on Cells and Tissues

Cellular Receptors for Tryptase

Tryptase as a Therapeutic Target

Acknowledgments

References

Section Six Nerve-Mast Cell Interactions: Physiology and Pathology

Chapter 20 Mast Cell-Nerve Interactions: Possible Significance of Nerve Growth Factor

Evidence for Mast Cell-Nerve Interactions

Possible Role of NGF

Acknowledgment

References

Chapter 21 Nerve Growth Factor, Mast Cells and Allergic Inflammation

Nerve Growth Factor: Early Discovery and Emerging Data

NGF and the Nervous System

NGF and the Endocrine System

NGF and the Immune System

NGF and Mast Cells

NGF and Inflammation

NGF and Allergic Responses

Behavioral Influence on NGF Levels and Allergic Responses

Possible Future Directions

Acknowledgments

References

Chapter 22 Interactions between Neurotrophins and Mast Cells

Definition and Basic Aspects of Neurotrophins

Mast Cells as a Source of Neurotrophic Factors

Effects of Neurotrophins on Mast Cells

Evidence that NGF is also a Human Mast Cell Growth Factor

Neurotrophin Receptors on Mast Cells

Clinical Findings Suggesting Mast Cell and Neurotrophin Activity

Mast Cells and Neurotrophins: Open Issues

Acknowledgment

References

Chapter 23 Modulation of Peripheral Neurotransmission Associated with Mast Cell Activation

Sensory (Afferent) Nervous System

Enteric Nervous System

Sympathetic Nervous System

Parasympathetic Nervous System

Summary

References

Chapter 24 Regulation of Gastrointestinal Mucin Production by Nerve-Mast Cell Interactions

Introduction

Neuronal Mediation of Mucin Secretion

Effects of Stress on Colonic Mucin and Prostaglandin Release

Role of Corticotropin-releasing Factor in Stress-induced Colonic Mucin Secretion

Neurotensin is an Important Mediator of Colonic Stress Responses

Mast Cells as a Major Link of Stress-mediated Mucin Secretion

CRF and NT as Mediators of Intestinal Mast Cell Activation During Stress

Clinical Implications

References

Section Seven Mast Cells and Basophils in Homeostasis and Host Defense

Chapter 25 Mast Cell-Enterobacteria Interactions during Infection

Introduction

Protective Role of Mast Cells Against Bacterial Infection

Mast Cell Phagocytosis of Bacteria

Molecular Basis for Mast Cell-Enterobacteria Recognition

Mast Cell Activation Via CD48

Interactions of Human Mast Cells with Enterobacteria

Final Thoughts

Acknowledgments

References

Chapter 26 Human Mast Cells and Basophils in Immune Responses to Infectious Agents

Introduction

Mast Cells in Host Defense Against Bacterial Infections

Mast Cells and Basophils in Helicobacterpylori Infection

Leukotrienes in the Defence against Bacterial and Viral Infections

Activation of Human Basophils and Mast Cells by Protein A

Activation of Human Basophils and Mast Cells by Protein L

Activation of Human Basophils by Pepstatin A

Endogenous Superallergen Protein Fv in Viral Hepatitis

Activation of Human Basophils and Mast Cells by HIV- 1 Glycoprotein gp120

The 'Three Faces' of Mast Cells and Basophils in the Immune Response to Infectious Agents

Acknowledgments

References

Chapter 27 Differential Regulation of Mast Cell Mediator Secretion by Bacterial Products

Introduction

Receptors for Bacteria on Mast Cells

Selective Mast Cell Responses to Specific Bacterial Products

Combined Signals Alter and Enhance Mast Cell Responses

Bacteria- and Bacterial Product-mediated Signaling Events in Mast Cells

Conclusions

References

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

Studies of Parasite Infection in Genetically Mast Cell-deficient Mice

Assessing the Role of IL-3 in Host Responses to Nematodes using IL-3-/-Mice

KitW/KitW-v, IL-3-/-Mice Exhibit a Profound Impairment of Basophilia, Mucosal Mast Cell Development and Immunity During Infection with Strongyloides venezuelensis

Summary

Acknowledgments

References

Section Eight Mast Cells in Atherosclerosis and Cardiac Diseases

Chapter 29 Human Heart Mast Cells: Immunological Characterization In Situ and In Vitro

Introduction

Isolation of HHMC and Their Characterization In Situ

Histamine, Proteolytic Enzymes and Proteoglycans Synthesized by HHMC

Prostaglandins and Cysteinyl Leukotrienes Synthesized De Novo by HMMC

Immunological and Non-immunological Stimuli that Activate HHMC In Vitro

Mast Cells and Regulation of Coagulation and Fibrinogenolysis

HHMC in Systemic and Cardiac Anaphylaxis and in Anaphylactoid Reactions

HHMC and Atherosclerosis

HHMC in Patients with Myocarditis and Hyper-eosinophilia

HHMC and Angiogenesis in the Heart

HHMC and Myocardial Ischaemia

HHMC in Idiopathic and Ischaemic Cardiomyopathy

Perspective and Conclusions

Acknowledgments

References

Chapter 30 Mast Cells in Atherosclerotic Human Coronary Arteries: Implications for Coronary Fatty Streak Formation, Plaque Ulceration and Control of Local Haemostatic Balance

Introduction

Atherosclerosis is a Disorder of Lipid Metabolism in the Arterial Intima with a Strong Inflammatory Component

Circulating Mast Cell Progenitors also find Their way in to the Arterial Intima

Immunohistochemical Observations on Mast Cells in the Human Coronary

Arterial Intima

Potential Mechanisms by Which Mast Cells may Play a Role in Atherogenesis

Conclusion and Future Directions

Acknowledgments

References

Chapter 31 Role of Mast Cells in Endogenous Fibrinolysis and Related (Patho)physiological Processes

Introduction

Contribution of Mast Cells to Fibrinogen Extravasation and Fibrin Formation

Mast Cell-dependent Fibrinolysis: Role of Tryptase and Chymase

The Mast Cell as Site of tPA Expression

Human Mast Cells Express the Urokinase Receptor (uPAR, CD87)

Functional Significance of MC-tPA: Mast Cells are 'Pro-fibrinolytic' Cells

Molecular Basis of Mast Cell Dependent Fibrinolysis: Role of Inhibitors (PAIs)

Fibrin-independent Plasminogen Activation

Clinical Significance

Mast Cells Accumulate at the Site of Thrombosis

SCF Regulates Expression and Release of tPA in Mast Cells

Concluding Remarks and Future Directions

Acknowledgment

References

Chapter 32 Mast Cells in Myocardial Ischaemia and Reperfusion

Introduction

Mast Cells in Normal Hearts

The Mast Cell as a Source of Cytokines

Mast Cell Degranulation Following Myocardial Ischaemia

Mast Cells in Healing Myocardial Infarcts

Mast Cell Precursors Infiltrate the Healing Heart

SCF Induction Following Myocardial Ischaemia/Reperfusion

Macrophages are the Main Source of SCF Following Myocardial Ischaemia

Potential Role of Mast Cells in Healing

The Mast Cell in Myocardial Ischaemia/Reperfusion: Friend or Foe?

Acknowledgment

References

Section Nine Leukotrienes, Cytokines and Chemokines in Allergic Disorders

Chapter 33 Lipid Mediators from Mast Cells and Basophils in Allergic Diseases

Introduction

Arachidonic Acid Pools in Human Mast Cells and Basophils

Phospholipase A 2 in Human Mast Cells and Basophils

Extracellular Effects of Mast Cell-derived Secretory PLA 2

PAF and Related Phospholipids

Concluding Remarks

Acknowledgments

References

Chapter 34 Regulation and Function of Human Intestinal Mast Cells

Introduction

Effector Functions of Human Intestinal Mast Cells

Regulation of Human Intestinal Mast Cell Functions

Clinical Implications

Future Directions

References

Chapter 35 Differential Regulation of Basophil Functions by Chemokines

Basophil Phenotype and Functions

Chemokines

Acknowledgment

References

Chapter 36 Chemokine Receptors on Human Mast Cells

Chemokines

Mast Cells

Chemokine Receptors on MC

Concluding Remarks

Acknowledgment

References

Chapter 37 Release and Cleavage of Stem Cell Factor by Human Mast Cells

Introduction

Stem Cell Factor Expression in Human Mast Cells

Stem Cell Factor-Protease Interactions

Biological Effects of SCF1-166 and SCF1-159 Oil HLMC and HSMC

Conclusions

Acknowledgments

References

Chapter 38 SCF-Induced Chemokine Production, Allergic Airway Inflammation and Airway Hyper-reactivity

Introduction

SCF-Induced Mast Cell Activation, Inflammation and Airway Hyper-reactivity

Regulation of SCF Production

Initiation of Cytokine/Chemokine Production by SCF in Mast Cells and Eosinophils

Structural Cell-derived SCF Contributes to Disease Progression: Differential Activation of Mast Cells by Soluble versus Membrane SCF

Summary

References

Section Ten Clinical Implications of Histamine H1 Receptor Antagonists

Chapter 39 Pharmacological Profile of Mizolastine, a Novel Histamine H1 Receptor Antagonist

Histamine and Its Receptor Subtypes

Specificity and Selectivity of Mizolastine for H1 Histamine Receptor Subtypes

Antihistaminergic Effects of Mizolastine

Allergic Reaction

Anti-anaphylactic Properties of Mizolastine

Immune System-mediated Inflammatory Reaction in Allergy

Anti-allergic Effects of Mizolastine

Other Pharmacological Effects of Mizolastine

Conclusion

Acknowledgment

References

Chapter 40 Adenosine-Induced Enhancement of Mast Cell Mediator Release in Asthma and COPD

Introduction

The Bronchoconstrictor Effect of Adenosine in Asthma

The Airway Response to Adenosine in COPD

Adenosine Receptors on Mast Cells

Concluding Comments

References

Chapter 41 Neural Activation and Inflammation in Allergic Rhinitis

Introduction

Neurogenic Inflammation

Neural Hyper-responsiveness

Nerve Growth Factor

Summary and Conclusion

References

Chapter 42 Antihistaminic and Anti-inflammatory Effects of Mizolastine

Introduction

Pharmacokinetics of Mizolastine

Clinical Efficacy of Mizolastine

Anti-inflammatory effects of Mizolastine

Concluding Remarks

References

Chapter 43 Electrophysiological and Molecular Basis for the Adverse Cardiovascular Effects of Histamine H, Receptor Antagonists

Introduction

Cardiotoxicity of Second-generation Antihistamines

Conclusions

Acknowledgments

References

Index