Airway Smooth Muscle in Asthma and COPD (eBook)

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

Airway Smooth Muscle 3
Contents 7
List of Contributors 13
1 Biophysical basis of airway smooth muscle contraction and hyperresponsiveness in asthma 17
1.1 Introduction 17
1.2 Airway hyperresponsiveness 18
1.3 Classical behaviour of airway smooth muscle and the balance of static forces 22
1.4 Shortening velocity and other manifestations of muscle dynamics 24
1.5 Biophysical characterization of airway smooth muscle: bronchospasm in culture? 26
1.6 Mechanical plasticity: a nonclassical feature of airway smooth muscle 30
1.7 Recent observations 34
1.8 Future directions 36
References 36
2 Dynamics of cytoskeletal and contractile protein organization: an emerging paradigm for airway smooth muscle contraction 47
2.1 Introduction 47
2.2 Molecular structure and organization of contractile and cytoskeletal filaments in the airway smooth muscle cell 49
2.3 Cytoskeletal dynamics and airway smooth muscle contraction 54
References 59
3 Airway smooth muscle: role in airway constrictor hyperresponsiveness 69
3.1 What is airway constrictor hyperresponsiveness (AHR)? 69
3.2 Is AHR ever good? 71
3.3 Potential mechanisms leading to airflow obstruction 71
3.4 Potential abnormalities of airway smooth muscle (ASM) 76
3.5 If ASM is dysfunctional, how did it get that way? 79
3.6 Summary 80
Acknowledgements 80
References 80
4 Airway smooth muscle phenotypic and functional plasticity 87
4.1 Introduction 87
4.2 Historical perspective: smooth muscle phenotype plasticity 88
4.3 Features of phenotype plasticity 90
4.4 Mechanisms for phenotypic plasticity 92
4.5 Functional plasticity of airway smooth muscle: role in asthma pathogenesis 96
4.6 Concluding remarks 100
References 100
5 Airway smooth muscle proliferation: insights into mechanisms regulating airway smooth muscle mass 105
5.1 Increases in airway smooth muscle (ASM) mass and the functional consequences 105
5.2 Growth factors, inflammatory mediators and cytokines modulate ASM proliferation 107
References 115
6 Airway smooth muscle bidirectional interactions with extracellular matrix 121
6.1 Overview 121
6.2 Introduction 122
6.3 Airway extracellular matrix (ECM) in health and disease 124
6.4 Integrins 126
6.5 Airway smooth muscle (ASM) as a modulator of airway ECM 127
6.6 Airway ECM as modulator of ASM function 129
6.7 Impact of anti-asthma therapy on ASM–ECM interactions 134
6.8 Conclusions 136
Acknowledgements 137
References 137
7 Airway smooth muscle interaction with mast cells 143
7.1 Introduction 143
7.2 Mast cell mediators alter smooth muscle function 145
7.3 Smooth muscle cells induce mast cell chemotaxis 148
7.4 Mast cells can adhere to airway smooth muscle 150
7.5 Conclusion 151
Acknowledgements 152
References 152
8 Airway smooth muscle synthesis of inflammatory mediators 157
8.1 Introduction 157
8.2 Lipid mediators 158
8.3 Chemokines 161
8.4 Growth and remodelling factors 165
8.5 Conclusions 168
References 168
9 Airway smooth muscle in experimental models 175
9.1 Introduction 175
9.2 Methods of assessment of airway smooth muscle (ASM) function 176
9.3 Potential mechanisms by which ASM properties may contribute to airway responsiveness 177
9.4 Experimental models 180
9.5 Conclusion 189
Acknowledgement 189
References 189
10 Altered properties of airway smooth muscle in asthma 197
10.1 Introduction 197
10.2 The extracellular matrix (ECM) and the airway smooth muscle (ASM) 198
10.3 ASM and integrins 206
10.4 The ASM cell and inflammation 207
10.5 The ASM cell and infection 209
References 210
11 The airway smooth muscle in chronic obstructive pulmonary disease (COPD) 217
11.1 Introduction 217
11.2 Definition and assessment of COPD 218
11.3 Pathological features of COPD 219
11.4 COPD mechanisms 222
11.5 Conclusion 236
References 236
12 Glucocorticoid actions on airway smooth muscle 251
12.1 Introduction 251
12.2 Airway smooth muscle (ASM) in airways disease 252
12.3 Gene induction by glucocorticoid receptors (GR) 256
12.4 Actions of B2-agonists and glucocorticoids on growth, proliferation, and migration of ASM 261
12.5 Summary and conclusions 264
Acknowledgements 264
References 264
13 B2-Adrenergic receptors: effects on airway smooth muscle 271
13.1 The B2-adrenoceptor 271
13.2 B2-Receptor activation 273
13.3 B2-Receptor signalling pathways 273
13.4 Effects in airway smooth muscle (ASM) 274
13.5 B2-Receptor desensitization 276
13.6 Influence of polymorphisms of the B2-adrenoceptor in ASM 278
13.7 Non-bronchodilator effects of B2-agonists in ASM 280
13.8 Conclusion 287
References 287
14 Asthma treatments: effects on the airway smooth muscle 293
14.1 Introduction 293
14.2 Role and abnormalities of airway smooth muscle (ASM) in asthma and COPD 295
14.3 Treatment of asthma 299
14.4 Conclusion 309
References 309
Index 319
Color Plates 329

"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." (Doody's Reviews, March 2009)