Airway Smooth Muscle in Asthma and COPD

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.

List of Contributors xi 1 Biophysical basis of airway smooth muscle contraction and hyperresponsiveness in asthma 1 Steven S. An and Jeffrey J. Fredberg 1.1 Introduction 1 1.2 Airway hyperresponsiveness 2 1.3 Classical behaviour of airway smooth muscle and the balance of static forces 6 1.4 Shortening velocity and other manifestations of muscle dynamics 8 1.5 Biophysical characterization of airway smooth muscle: bronchospasm in culture? 10 1.6 Mechanical plasticity: a nonclassical feature of airway smooth muscle 14 1.7 Recent observations 18 1.8 Future directions 20 References 20 2 Dynamics of cytoskeletal and contractile protein organization: an emerging paradigm for airway smooth muscle contraction 31 Wenwu Zhang and Susan J. Gunst 2.1 Introduction 31 2.2 Molecular structure and organization of contractile and cytoskeletal filaments in the airway smooth muscle cell 33 2.3 Cytoskeletal dynamics and airway smooth muscle contraction 38 References 43 3 Airway smooth muscle: role in airway constrictor hyperresponsiveness 53 Melanie Brown and Julian Solway 3.1 What is airway constrictor hyperresponsiveness (AHR)? 53 3.2 Is AHR ever good? 55 3.3 Potential mechanisms leading to airflow obstruction 55 3.4 Potential abnormalities of airway smooth muscle (ASM) 60 3.5 If ASM is dysfunctional, how did it get that way? 63 3.6 Summary 64 Acknowledgements 64 References 64 4 Airway smooth muscle phenotypic and functional plasticity 71 Andrew J. Halayko, Reinoud Gosens and Thai Tran 4.1 Introduction 71 4.2 Historical perspective: smooth muscle phenotype plasticity 72 4.3 Features of phenotype plasticity 74 4.4 Mechanisms for phenotypic plasticity 76 4.5 Functional plasticity of airway smooth muscle: role in asthma pathogenesis 80 4.6 Concluding remarks 84 References 84 5 Airway smooth muscle proliferation: insights into mechanisms regulating airway smooth muscle mass 89 Reynold A. Panettieri, Jr. 5.1 Increases in airway smooth muscle (ASM) mass and the functional consequences 89 5.2 Growth factors, inflammatory mediators and cytokines modulate ASM proliferation 91 References 99 6 Airway smooth muscle bidirectional interactions with extracellular matrix 105 Jane E. Ward and Stuart J. Hirst 6.1 Overview 105 6.2 Introduction 106 6.3 Airway extracellular matrix (ECM) in health and disease 108 6.4 Integrins 110 6.5 Airway smooth muscle (ASM) as a modulator of airway ECM 111 6.6 Airway ECM as modulator of ASM function 113 6.7 Impact of anti-asthma therapy on ASM–ECM interactions 118 6.8 Conclusions 120 Acknowledgements 121 References 121 7 Airway smooth muscle interaction with mast cells 127 Roger Marthan, Patrick Berger, Pierre-Olivier Girodet and J. Manuel Tunon-de-Lara 7.1 Introduction 127 7.2 Mast cell mediators alter smooth muscle function 129 7.3 Smooth muscle cells induce mast cell chemotaxis 132 7.4 Mast cells can adhere to airway smooth muscle 134 7.5 Conclusion 135 Acknowledgements 136 References 136 8 Airway smooth muscle synthesis of inflammatory mediators 141 Alison E. John, Deborah L. Clarke, Alan J. Knox and Karl Deacon 8.1 Introduction 141 8.2 Lipid mediators 142 8.3 Chemokines 146 8.4 Growth and remodelling factors 149 8.5 Conclusions 152 References 152 9 Airway smooth muscle in experimental models 159 Anne-Marie Lauzon and James G. Martin 9.1 Introduction 159 9.2 Methods of assessment of airway smooth muscle (ASM) function 160 9.3 Potential mechanisms by which ASM properties may contribute to airway responsiveness 161 9.4 Experimental models 164 9.5 Conclusion 173 Acknowledgement 173 References 173 10 Altered properties of airway smooth muscle in asthma 181 Judith Black, Janette Burgess, Brian Oliver and Lyn Moir 10.1 Introduction 181 10.2 The extracellular matrix (ECM) and the airway smooth muscle (ASM) 182 10.3 ASM and integrins 190 10.4 The ASM cell and inflammation 191 10.5 The ASM cell and infection 193 References 194 11 The airway smooth muscle in chronic obstructive pulmonary disease (COPD) 201 Maria B. Sukkar and Kian Fan Chung 11.1 Introduction 201 11.2 Definition and assessment of COPD 202 11.3 Pathological features of COPD 203 11.4 COPD mechanisms 206 11.5 Conclusion 220 References 220 12 Glucocorticoid actions on airway smooth muscle 235 Ian M. Adcock, Loukia Tsaprouni and Pank Bhavsar 12.1 Introduction 235 12.2 Airway smooth muscle (ASM) in airways disease 236 12.3 Gene induction by glucocorticoid receptors (GR) 240 12.4 Actions of β2-agonists and glucocorticoids on growth, proliferation, and migration of ASM 245 12.5 Summary and conclusions 248 Acknowledgements 248 References 248 13 β2-Adrenergic receptors: effects on airway smooth muscle 255 Malcolm Johnson 13.1 The β2-adrenoceptor 255 13.2 β2-Receptor activation 257 13.3 β2-Receptor signalling pathways 257 13.4 Effects in airway smooth muscle (ASM) 258 13.5 β2-Receptor desensitization 260 13.6 Influence of polymorphisms of the β2-adrenoceptor in ASM 262 13.7 Non-bronchodilator effects of β2-agonists in ASM 264 13.8 Conclusion 271 References 271 14 Asthma treatments: effects on the airway smooth muscle 277 Kian Fan Chung 14.1 Introduction 277 14.2 Role and abnormalities of airway smooth muscle (ASM) in asthma and COPD 279 14.3 Treatment of asthma 283 14.4 Conclusion 293 References 293 Index 303