Cells in focus
Airway smooth muscle: contraction and beyond

https://doi.org/10.1016/S1357-2725(02)00259-5Get rights and content

Abstract

Airway smooth muscle (ASM), an important tissue involved in the regulation of bronchomotor tone, exists in the trachea and in the bronchial tree up to the terminal bronchioles. The physiological relevance of ASM in healthy airways remains unclear. Evidence, however, suggests that ASM undergoes marked phenotypic modulation in lung development and in disease states such as asthma, chronic bronchitis and emphysema. The shortening of ASM regulates airway luminal diameter and modulates airway resistance, which can be augmented by cytokines as well as extracellular matrix alterations. ASM may also serve immunomodulatory functions, which are mediated by the secretion of pro-inflammatory mediators such as cytokines and chemokines. In addition, ASM mass increases in chronic airway diseases and may represent either a pathologic or an injury-repair response due to chronic inflammation. This review will present evidence that ASM, a “passive” contractile tissue, may become an “active participant” in modulating inflammation in chronic lung diseases.

Cell facts

  • Found in the trachea and along the bronchial tree.

  • Critically important in regulating bronchomotor tone of the airways.

  • Differentiation state is associated with the expression of various “contractile proteins.”

  • Displays phenotypic modulation of mechanical, synthetic and proliferative responses.

  • Secretes cytokines, chemokines and extracellular matrix proteins.

  • May serve as a potential new target for the treatment of chronic lung diseases.

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)

  • Y. Yang et al.

    Stretch-induced alternative splicing of serum response factor promotes bronchial myogenesis and is defective in lung hypoplasia

    J. Clin. Invest.

    (2000)
  • R. Ramchandani et al.

    Differences in airway structure in immature and mature rabbits

    J. Appl. Physiol.

    (2000)
  • P.R. Johnson et al.

    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.

    (2000)
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