The International Journal of Biochemistry & Cell Biology
Cells in focusAirway smooth muscle: contraction and beyond
Introduction
Anatomically, airway smooth muscle (ASM) circumferentially surrounds the lumen of the bronchi; however, the precise function of ASM remains unclear. In the upper airway ASM is found in the posterior aspect of the trachea attached to cartilage. In the lower airways ASM is oriented in a helix–antihelix pattern encasing the bronchi. The orientation of ASM in the lower airways suggests a highly efficient architectural structure that greatly enhances the ability of the muscle to sustain bronchoconstriction. In the upper airways, ASM accounts for approximately 25% of the cellular mass while in the lower airways, ASM constitutes 4–5% of the cellular mass. Although microscopically ASM of the upper and lower airways appears similar [1], there likely exists heterogeneity with regard to the cells that compose ASM as evidenced by the differential distribution of β-adrenergic receptor expression on ASM from the upper airways compared to lower airways.
Section snippets
Cell origin and development
Smooth muscle that resides in the vasculature and other organ systems morphologically appears similar; there are, however, dramatic developmental differences between ASM and other visceral smooth muscle such as vascular smooth muscle [2], [3]. During embryogenesis, ASM development occurs earlier than that of vascular smooth muscle. In addition, in contrast to skeletal and cardiac muscle derived from mesodermal precursors, ASM appears to originate from neural crest cells and mesenchymal cells.
ASM function in health and disease
Although the role of mature ASM in the healthy state remains known, evidence suggests that changes in ASM phenotype may play a fundamental role in the pathogenesis of lung diseases (Fig. 1).
Conclusion and future directions
ASM is a dynamic and complex mesenchymal cell whose normal contractile activity in mature tissues is determined by internal components (contractile apparatus and regulatory proteins) and external factors (mechanical forces, ECM proteins, nerves). Modulation of these regulatory factors is likely to lead to phenotypic changes of the ASM that may play a role in the pathogenesis of chronic airway disease. On the basis of these observations, it is reasonable to hypothesize that targeting the
Acknowledgements
The authors wish to acknowledge the helpful suggestions of Dr. Andrew Halayko. This work was supported by NIH Grants 2R01-HL55301 (RAP) and 1P50-HL67663 (RAP), and by an American Lung Association Grant RG-062-N (YA). Yassine Amrani is a Parker B. Francis Fellow in Pulmonary Research.
References (26)
- et al.
Lung smooth muscle differentiation
Int. J. Biochem. Cell Biol.
(1998) - et al.
The IL-5 receptor on human bronchus selectively primes for hyperresponsiveness
J. Allergy Clin. Immunol.
(2002) - et al.
Airway muscle in preterm infants: changes during development
J. Pediatr.
(1997) - et al.
Airway smooth muscle as an immunomodulatory cell: a new target for pharmacotherapy
Curr. Opin. Pharmacol.
(2001) - et al.
The contractile apparatus and mechanical properties of airway smooth muscle
Eur. Respir. J.
(2000) Molecular control of vascular smooth muscle cell differentiation
Acta Physiol. Scand.
(1998)- et al.
Molecular mechanisms of phenotypic plasticity in smooth muscle cells
J. Appl. Physiol.
(2001) Spontaneous rhythmical contraction of the muscles of the bronchial tubes and air sacs of the chick embryo
Am. J. Physiol.
(1924)- et al.
Spontaneous peristaltic airway contractions propel lung liquid through the bronchial tree of intact and fetal lung explants
Am. J. Respir. Cell Mol. Biol.
(2000) - et al.
Role of laminin polymerization at the epithelial mesenchymal interface in bronchial myogenesis
Development
(1998)
Stretch-induced alternative splicing of serum response factor promotes bronchial myogenesis and is defective in lung hypoplasia
J. Clin. Invest.
Differences in airway structure in immature and mature rabbits
J. Appl. Physiol.
The production of extracellular matrix proteins by human passively sensitized airway smooth-muscle cells in culture: the effect of beclomethasone
Am. J. Respir. Crit. Care Med.
Cited by (68)
Stressed out - The role of oxidative stress in airway smooth muscle dysfunction in asthma and COPD
2022, Free Radical Biology and MedicineCitation Excerpt :COPD is characterised by respiratory symptoms including breathlessness, cough and sputum production accompanied by airflow limitation resulting from pathophysiological changes to the airways and/or alveoli [3]. The ASM is present throughout the bronchial tree surrounding the airways in two opposing spirals, as well as the posterior of the trachea [4]. Although its role in healthy adults remains unclear, the dysfunction of ASM is known to contribute to symptoms and decline in lung function in asthma and COPD via contractile dysfunction, release of inflammatory mediators and increased ASM mass, and is a key contributor to symptoms in patients that remain symptomatic despite optimal provision of currently available treatments [4–6].
Neonatal Streptococcus Pneumoniae pneumonia induces airway SMMHC expression through HMGB1/TLR4/ERK
2021, Immunology LettersCitation Excerpt :SMMHC was found overexpressed in airway biopsies of both asthma patients’ and animal model, knocking down SMMHC in mice slows down the time course of bronchoconstriction [11,12]. These suggest the pivotal role of SMMHC in promoting airway hyperresponsiveness (AHR) and asthma development [13,14]. Our previous study stated that neonatal S. pneumoniae pneumonia promoted SMMHC expression significantly and contributed to AHR and asthma development in mice model [15,16].
Therapeutic targets in lung tissue remodelling and fibrosis
2021, Pharmacology and TherapeuticsCell-specific drug targeting in the lung
2021, Biochemical PharmacologyCitation Excerpt :The physiological relevance of ASMCs in healthy airways remains unclear. Evidence, however, suggests that ASMCs undergoes marked phenotypic modulation in lung development and in disease states such as asthma and COPD [99]. Asthma is a complex inflammatory disease of the airways involving reversible bronchoconstriction.
Neural Control of Airway Smooth Muscle
2021, Encyclopedia of Respiratory Medicine, Second Edition