Airway Smooth Muscle in Asthma and COPD

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

• List of Contributors xi1 Biophysical basis of airway smooth muscle contraction and hyperresponsiveness in asthma 1Steven S. An and Jeffrey J. Fredberg1.1 Introduction 11.2 Airway hyperresponsiveness 21.3 Classical behaviour of airway smooth muscle and the balance of static forces 61.4 Shortening velocity and other manifestations of muscle dynamics 81.5 Biophysical characterization of airway smooth muscle: bronchospasm in culture? 101.6 Mechanical plasticity: a nonclassical feature of airway smooth muscle 141.7 Recent observations 181.8 Future directions 20References 202 Dynamics of cytoskeletal and contractile protein organization: an emerging paradigm for airway smooth muscle contraction 31Wenwu Zhang and Susan J. Gunst2.1 Introduction 312.2 Molecular structure and organization of contractile and cytoskeletal filaments in the airway smooth muscle cell 332.3 Cytoskeletal dynamics and airway smooth muscle contraction 38References 433 Airway smooth muscle: role in airway constrictor hyperresponsiveness 53Melanie Brown and Julian Solway3.1 What is airway constrictor hyperresponsiveness (AHR)? 533.2 Is AHR ever good? 553.3 Potential mechanisms leading to airflow obstruction 553.4 Potential abnormalities of airway smooth muscle (ASM) 603.5 If ASM is dysfunctional, how did it get that way? 633.6 Summary 64Acknowledgements 64References 644 Airway smooth muscle phenotypic and functional plasticity 71Andrew J. Halayko, Reinoud Gosens and Thai Tran4.1 Introduction 714.2 Historical perspective: smooth muscle phenotype plasticity 724.3 Features of phenotype plasticity 744.4 Mechanisms for phenotypic plasticity 764.5 Functional plasticity of airway smooth muscle: role in asthma pathogenesis 804.6 Concluding remarks 84References 845 Airway smooth muscle proliferation: insights into mechanisms regulating airway smooth muscle mass 89Reynold A. Panettieri, Jr.5.1 Increases in airway smooth muscle (ASM) mass and the functional consequences 895.2 Growth factors, inflammatory mediators and cytokines modulate ASM proliferation 91References 996 Airway smooth muscle bidirectional interactions with extracellular matrix 105Jane E. Ward and Stuart J. Hirst6.1 Overview 1056.2 Introduction 1066.3 Airway extracellular matrix (ECM) in health and disease 1086.4 Integrins 1106.5 Airway smooth muscle (ASM) as a modulator of airway ECM 1116.6 Airway ECM as modulator of ASM function 1136.7 Impact of anti-asthma therapy on ASM–ECM interactions 1186.8 Conclusions 120Acknowledgements 121References 1217 Airway smooth muscle interaction with mast cells 127Roger Marthan, Patrick Berger, Pierre-Olivier Girodet and J. Manuel Tunon-de-Lara7.1 Introduction 1277.2 Mast cell mediators alter smooth muscle function 1297.3 Smooth muscle cells induce mast cell chemotaxis 1327.4 Mast cells can adhere to airway smooth muscle 1347.5 Conclusion 135Acknowledgements 136References 1368 Airway smooth muscle synthesis of inflammatory mediators 141Alison E. John, Deborah L. Clarke, Alan J. Knox and Karl Deacon8.1 Introduction 1418.2 Lipid mediators 1428.3 Chemokines 1468.4 Growth and remodelling factors 1498.5 Conclusions 152References 1529 Airway smooth muscle in experimental models 159Anne-Marie Lauzon and James G. Martin9.1 Introduction 1599.2 Methods of assessment of airway smooth muscle (ASM) function 1609.3 Potential mechanisms by which ASM properties may contribute to airway responsiveness 1619.4 Experimental models 1649.5 Conclusion 173Acknowledgement 173References 17310 Altered properties of airway smooth muscle in asthma 181Judith Black, Janette Burgess, Brian Oliver and Lyn Moir10.1 Introduction 18110.2 The extracellular matrix (ECM) and the airway smooth muscle (ASM) 18210.3 ASM and integrins 19010.4 The ASM cell and inflammation 19110.5 The ASM cell and infection 193References 19411 The airway smooth muscle in chronic obstructive pulmonary disease (COPD) 201Maria B. Sukkar and Kian Fan Chung11.1 Introduction 20111.2 Definition and assessment of COPD 20211.3 Pathological features of COPD 20311.4 COPD mechanisms 20611.5 Conclusion 220References 22012 Glucocorticoid actions on airway smooth muscle 235Ian M. Adcock, Loukia Tsaprouni and Pank Bhavsar12.1 Introduction 23512.2 Airway smooth muscle (ASM) in airways disease 23612.3 Gene induction by glucocorticoid receptors (GR) 24012.4 Actions of β2-agonists and glucocorticoids on growth, proliferation, and migration of ASM 24512.5 Summary and conclusions 248Acknowledgements 248References 24813 β2-Adrenergic receptors: effects on airway smooth muscle 255Malcolm Johnson13.1 The β2-adrenoceptor 25513.2 β2-Receptor activation 25713.3 β2-Receptor signalling pathways 25713.4 Effects in airway smooth muscle (ASM) 25813.5 β2-Receptor desensitization 26013.6 Influence of polymorphisms of the β2-adrenoceptor in ASM 26213.7 Non-bronchodilator effects of β2-agonists in ASM 26413.8 Conclusion 271References 27114 Asthma treatments: effects on the airway smooth muscle 277Kian Fan Chung14.1 Introduction 27714.2 Role and abnormalities of airway smooth muscle (ASM) in asthma and COPD 27914.3 Treatment of asthma 28314.4 Conclusion 293References 293Index 303

“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)