Airway Smooth Muscle in Asthma and COPD Biology and Pharmacology

by Chung, Kian Fan

• ISBN13: 9780470060667
• ISBN10: 0470060662
• Edition: 1st
• Format: Hardcover
• Copyright: 2008-05-27
• Publisher: Wiley

Summary

In this book, leading researchers in medicine and molecular pharmacology explain the cellular mechanisms that control airway smooth muscle. The means by which these are disrupted in disease, and the pharmacologic strategies by which they may be modified are discussed and future therapeutic interventions are identified.Aimed at specialists in pulmonology, this volume provides the clinician with the most up to date information on one of the core physiological processes in airway disease, and offers insights into current and future approaches to management.Authoritative update on key mechanisms of airway constriction in Asthma and COPD Relates latest research to bronchodilator therapy Multi-contributed text, co-coordinated by two of the leading authorities in the field.

Author Biography

K Fan Chung, Professor, Experimental Studies Group, Royal Brompton Campus; Editorial Board member of American Journal Respiratory Critical Care Medicine, Respirology

Table of Contents

List of Contributors	p. xi
Biophysical basis of airway smooth muscle contraction and hyperresponsiveness in asthma	p. 1
Introduction	p. 1
Airway hyperresponsiveness	p. 2
Classical behaviour of airway smooth muscle and the balance of static forces	p. 6
Shortening velocity and other manifestations of muscle dynamics	p. 8
Biophysical characterization of airway smooth muscle: bronchospasm in culture?	p. 10
Mechanical plasticity: a nonclassical feature of airway smooth muscle	p. 14
Recent observations	p. 18
Future directions	p. 20
References	p. 20
Dynamics of cytoskeletal and contractile protein organization: an emerging paradigm for airway smooth muscle contraction	p. 31
Introduction	p. 31
Molecular structure and organization of contractile and cytoskeletal filaments in the airway smooth muscle cell	p. 33
Cytoskeletal dynamics and airway smooth muscle contraction	p. 38
References	p. 43
Airway smooth muscle: role in airway constrictor hyperresponsiveness	p. 53
What is airway constrictor hyperresponsiveness (AHR)?	p. 53
Is AHR ever good?	p. 55
Potential mechanisms leading to airflow obstruction	p. 55
Potential abnormalities of airway smooth muscle (ASM)	p. 60
If ASM is dysfunctional, how did it get that way?	p. 63
Summary	p. 64
Acknowledgements	p. 64
References	p. 64
Airway smooth muscle phenotypic and functional plasticity	p. 71
Introduction	p. 71
Historical perspective: smooth muscle phenotype plasticity	p. 72
Features of phenotype plasticity	p. 74
Mechanisms for phenotypic plasticity	p. 76
Functional plasticity of airway smooth muscle: role in asthma pathogenesis	p. 80
Concluding remarks	p. 84
References	p. 84
Airway smooth muscle proliferation: insights into mechanisms regulating airway smooth muscle mass	p. 89
Increases in airway smooth muscle (ASM) mass and the functional consequences	p. 89
Growth factors, inflammatory mediators and cytokines modulate ASM proliferation	p. 91
References	p. 99
Airway smooth muscle bidirectional interactions with extracellular matrix	p. 105
Overview	p. 105
Introduction	p. 106
Airway extracellular matrix (ECM) in health and disease	p. 108
Integrins	p. 110
Airway smooth muscle (ASM) as a modulator of airway ECM	p. 111
Airway ECM as modulator of ASM function	p. 113
Impact of anti-asthma therapy on ASM-ECM interactions	p. 118
Conclusions	p. 120
Acknowledgements	p. 121
References	p. 121
Airway smooth muscle interaction with mast cells	p. 127
Introduction	p. 127
Mast cell mediators alter smooth muscle function	p. 129
Smooth muscle cells induce mast cell chemotaxis	p. 132
Mast cells can adhere to airway smooth muscle	p. 134
Conclusion	p. 135
Acknowledgements	p. 136
References	p. 136
Airway smooth muscle synthesis of inflammatory mediator	p. 141
Introduction	p. 141
Lipid mediators	p. 142
Chemokines	p. 146
Growth and remodelling factors	p. 149
Conclusions	p. 152
References	p. 152
Airway smooth muscle in experimental models	p. 159
Introduction	p. 159
Methods of assessment of airway smooth muscle (ASM) function	p. 160
Potential mechanisms by which ASM properties may contribute to airway responsiveness	p. 161
Experimental models	p. 164
Conclusion	p. 173
Acknowledgement	p. 173
References	p. 173
Altered properties of airway smooth muscle in asthma	p. 181
Introduction	p. 181
The extracellular matrix (ECM) and the airway smooth muscle (ASM)	p. 182
ASM and integrins	p. 190
The ASM cell and inflammation	p. 191
The ASM cell and infection	p. 193
References	p. 194
The airway smooth muscle in chronic obstructive pulmonary disease (COPD)	p. 201
Introduction	p. 201
Definition and assessment of COPD	p. 202
Pathological features of COPD	p. 203
COPD mechanisms	p. 206
Conclusion	p. 220
References	p. 220
Glucocorticoid actions on airway smooth muscle	p. 235
Introduction	p. 235
Airway smooth muscle (ASM) in airways disease	p. 236
Gene induction by glucocorticoid receptors (GR)	p. 240
Actions of [beta subscript 2]-agonists and glucocorticoids on growth, proliferation, and migration of ASM	p. 245
Summary and conclusions	p. 248
Acknowledgements	p. 248
References	p. 248
[beta subscript 2]-Adrenergic receptors: effects on airway smooth muscle	p. 255
The [beta subscript 2]-adrenoceptor	p. 255
[beta subscript 2]-Receptor activation	p. 257
[beta subscript 2]-Receptor signalling pathways	p. 257
Effects in airway smooth muscle (ASM)	p. 258
[beta subscript 2]-Receptor desensitization	p. 260
Influence of polymorphisms of the [beta subscript 2]-adrenoceptor in ASM	p. 262
Non-bronchodilator effects of [beta subscript 2]-agonists in ASM	p. 264
Conclusion	p. 271
References	p. 271
Asthma treatments: effects on the airway smooth muscle	p. 277
Introduction	p. 277
Role and abnormalities of airway smooth muscle (ASM) in asthma and COPD	p. 279
Treatment of asthma	p. 283
Conclusion	p. 293
References	p. 293
Index	p. 303
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