Airway Smooth Muscle in Asthma and COPD – Biology and Pharmacology

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

List of Contributors. 1. Biophysical basis of airway smooth muscle contraction and hyperresponsiveness in asthma (Steven S. An and Jefferey J. Fredberg). 1.1 Introduction. 1.2 Airway hyperresponsiveness. 1.3 Classical behaviour of airway smooth muscle and the balance of static forces. 1.4 Shortening velocity and other manifestations of muscle dynamics. 1.5 Biophysical characterization of airway smooth muscle: bronchospasm in culture? 1.6 Mechanical plasticity: a nonclassical feature of airway smooth muscle. 1.7 Recent observations. 1.8 Future directions. References. 2. Dynamics of cytoskeletal and contractile protein organization: an emerging paradigm for airway smooth muscle contraction (Wenwu Zhang and Susan J. Gunst). 2.1 Introduction. 2.2 Molecular structure and organization of contractile and cytoskeletal filaments in the airway smooth muscle cell. 2.3 Cytoskeletal dynamics and airway smooth muscle contraction. References. 3. Airway smooth muscle: role in airway constrictor hyperresponsiveness (Melanie Brown and Julian Solway). 3.1 What is airway constrictor hyperresponsiveness (AHR)? 3.2 IS AHR ever good? 3.3 Potential mechanisms leading to airflow obstruction. 3.4 Potential abnormalities of airway smooth muscle (ASM). 3.5 If ASM is dysfunctional, how did it get that way? 3.6 Summary. Acknowledgements. References. 4. Airway smooth muscle phenotypic and functional plasticity (Andrew J. Halayko, Reinoud Gosens and Thai Tran). 4.1 Introduction. 4.2 Historical perspective: smooth muscle phenotype plasticity. 4.3 Features of phenotype plasticity. 4.4 Mechanisms for phenotypic plasticity. 4.5 Functional plasticity of airway smooth muscle: role in asthma pathogenesis. 4.6 Concluding remarks. References. 5. Airway smooth muscle proliferation: insights into mechanisms regulating airway smooth muscle mass (Reynold A. Panettieri, Jr.). 5.1 Increases in airway smooth muscle (ASM) mass and the functional consequences. 5.2 Growth factors, inflammatory mediators and cytokines modulate ASM proliferation. References. 6. Airway smooth muscle bidirectional interactions with extracellular matrix (Jane E. Ward and Stuart J. Hirst). 6.1 Overview 6.2 Introduction 6.3 Airway extracellular matrix (ECM) in health and disease. 6.4 Integrins. 6.5 Airway smooth muscle (ASM) as a modulator of airway ECM. 6.6 Airway ECM as modulator of ASM function. 6.7 Impact of anti-asthma therapy on ASM-ECM interactions. 6.8 Conclusions. Acknowledgements. References. 7. Airway smooth muscle interaction with mast cells (Roger Marthan, Patrick Berger, Pierre-Olivier Girodet and J. Manuel Tunon-de-Lara). 7.1 Introduction. 7.2 Mast Cell mediators after smooth muscle function. 7.3 Smooth muscle cells induce mast cell chemotaxis. 7.4 Mast cells can adhere to airway smooth muscle. 7.5 Conclusion. Acknowledgements. References. 8. Airway smooth muscle synthesis of inflammatory mediators (Alison E. John, Deborah L. Clarke, Alan J. Knox and Karl Deacon). 8.1 Introduction. 8.2 Lipid mediators. 8.3 Chemokines. 8.4 Growth and remodelling factors. 8.5 Conclusions. References. 9. Airway smooth muscle in experimental models (Anne-Marie Lauzon and James G. Martin). 9.1 Introduction. 9.2 Methods of assessment of airway smooth muscle (ASM) function. 9.3 Potential mechanisms by which ASM properties may contribute to airway responsiveness. 9.4 Experimental models. 9.5 Conclusion. Acknowledgement. References. 10. Altered properties of airway smooth muscle in asthma (Judith Black, Janette Burgess, Brian Oliver and Lyn Moir). 10.1 Introduction. 10.2 The extracellular matrix (ECM) and the airway smooth muscle (ASM). 10.3 ASM and integrins. 10.4 The ASM cell and inflammation. 10.5 The ASM cell and infection. References. 11. The airway smooth muscle in chronic obstructive pulmonary disease (COPD) (Maria B. Sukkar and Kian Fan Chung). 11.1 Introduction. 11.2 Definition and assessment of COPD. 11.3 Pathological features of COPD. 11.4 COPD mechanisms. 11.5 Conclusion. References. 12. Glucocorticoid actions on airway smooth muscle (Ian M. Adcock, Loukia Tsaprouni and Pank Bhavsar). 12.1 Introduction. 12.2 Airway smooth muscle (ASM) in airways disease. 12.3 Gene introduction by glucocorticoid receptors (GR). 12.4 Actions of s2-agonists and glucocorticoids on growth, proliferation, and migration of ASM. 12.5 Summary and conclusions. Acknowledgements. References. 13. s2-Adrenergic receptors: effects on airway smooth muscle (Malcolm Johnson). 13.1 The s2-adrenoceptor. 13.2 s2-Receptor activation. 13.3 s2-Receptor signalling pathways. 13.4 Effects in airway smooth muscle (ASM). 13.5 s2-Receptor desensitization. 13.6 Influence of polymorphisms of the s2-adrenoceptor in ASM. 13.7 Non-bronchodilator effects of s2-agonists in ASM. 13.8 Conclusion. References. 14. Asthma treatments: effects on the airway smooth muscle (Kian Fan Chung). 14.1 Introduction. 14.2 Role and abnormalities of airway smooth muscle (ASM) in asthma and COPD. 14.3 Treatment of asthma. 14.4 References. Index.