Journal of Allergy and Clinical Immunology
Airway smooth muscle function in asthma and COPDSynthetic responses in airway smooth muscle☆
Section snippets
Extracellular matrix and ASM in asthma
The term extracellular matrix encompasses all that is not cellular within tissue and includes both basement membrane connective tissue and interstitial connective tissue (Fig 2). The interstitial extracellular matrix (ECM) surrounds ASM, and there are bidirectional interactions: human ASM has synthetic capabilities of modulating ECM, and the composition of the ECM can influence ASM responses to stimulation, affecting its proliferative, migratory, and synthetic capabilities (Fig 3). Exposure of
Chemokine and cytokine production by ASM
When an inflammatory process is initiated in an organ such as the lung, low-molecular-weight cytokines (chemokines) are produced that are responsible for recruiting inflammatory cells along diffusion gradients (Fig 4). Chemokines, which can be divided into several categories on the basis of their molecular structure,21 exhibit a degree of selectivity for distinct inflammatory cell populations. For example, eotaxin, RANTES, and IL-5 have been primarily considered to recruit eosinophils, although
Autocrine regulation of ASM function
As described, various T-cell–derived and mast cell–derived cytokines present in high levels in asthmatic airways, such as IL-4, IL-5, IL-13, and TNF-α, are believed to orchestrate both acute and chronic inflammatory responses by altering myocyte function.59., 60. Although airway remodeling may be influenced by cytokines acting indirectly by promoting the recruitment, activation, and trafficking of leukocytes, evidence now suggests that cytokines may also exert paracrine or autocrine effects by
ASM: a target for β2-agonist/corticosteroid interactions
β2-Agonists and corticosteroids are widely used in the treatment of bronchial asthma and COPD. The combination of LABAs and inhaled corticosteroids (ICSs) results in improved lung function, better symptom control, and reduced exacerbations compared with LABAs or higher doses of ICSs alone.121., 122. Several studies have shown that LABAs potentiate the anti-inflammatory actions of corticosteroids in either an additive or a synergistic manner.123., 124. Recent evidence suggests that ASM cells may
Summary and implications for future research
Airway smooth muscle clearly can contribute to the formation of the ECM, and in this respect, ASM from asthmatic patients has both qualitative and quantitative differences in its response to stimuli. Thus, the ASM cells are important regulating cells potentially contributing to the known alterations within the ECM in asthma. In addition, through integrin-directed signaling, ECM components can change human ASM function, altering the proliferative, survival, and cytoskeletal synthetic function.
Acknowledgements
Dr Knox thanks Dan Duthie for help with graphics.
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Disclosure of potential conflict of interest: A. J. Knox has consultant arrangements with GlaxoSmithKline and Astra Zeneca; he receives grants/research support from GlaxoSmithKline. Y. Amrani receives grants/research support from NIH and Centocor; he is employed by the University of Pennsylvania. R. A. Panettieri has consultant arrangements with Merck, GlaxoSmithKline, Schering, and Epigenesis; he receives grants/research support from Merck, GlaxoSmithKline, and Centocor; is employed by the University of Pennsylvania; and is on the Speakers' Bureau of Merck, GlaxoSmithKline, Schering, and Epigenesis. M. Johnson is employed by GlaxoSmithKline Research and Development. P. H. Howarth and O. Tliba have no conflict of interest to disclose.
Supported by the Medical Research Council, the Wellcome Trust, the National Asthma Campaign, and Glaxo Smith Kline (Dr Knox); National Institutes of Health grants 2R01-HL55301 and 1P50-HL67663 (Dr Panettieri); and American Lung Association grant RG-062-N (Dr Amrani). Dr Amrani is a Parker B. Francis Fellow in Pulmonary Research.