scholarly journals Accumulating Evidence for Increased Velocity of Airway Smooth Muscle Shortening in Asthmatic Airway Hyperresponsiveness

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Gijs Ijpma ◽  
Oleg Matusovsky ◽  
Anne-Marie Lauzon
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Normal Subjects ◽  
Shortening Velocity ◽  
Tissue Samples ◽  
Velocity Increase ◽  
Human Lungs ◽  
Velocity Of Shortening ◽  
Muscle Shortening

It remains unclear whether airway smooth muscle (ASM) mechanics is altered in asthma. While efforts have originally focussed on contractile force, some evidence points to an increased velocity of shortening. A greater rate of airway renarrowing after a deep inspiration has been reported in asthmatics compared to controls, which could result from a shortening velocity increase. In addition, we have recently shown in rats that increased shortening velocity correlates with increased muscle shortening, without increasing muscle force. Nonetheless, establishing whether or not asthmatic ASM shortens faster than that of normal subjects remains problematic. Endobronchial biopsies provide excellent tissue samples because the patients are well characterized, but the size of the samples allows only cell level experiments. Whole human lungs from transplant programs suffer primarily from poor patient characterization, leading to high variability. ASM from several animal models of asthma has shown increased shortening velocity, but it is unclear whether this is representative of human asthma. Several candidates have been suggested as responsible for increased shortening velocity in asthma, such as alterations in contractile protein expression or changes in the contractile apparatus structure. There is no doubt that more remains to be learned about the role of shortening velocity in asthma.

Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation

1997 ◽  
Vol 83 (3) ◽  
pp. 739-745 ◽  
Author(s):  
X. Shen ◽  
M. F. Wu ◽  
R. S. Tepper ◽  
S. J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Mechanical Response ◽  
Isometric Force ◽  
Shortening Velocity ◽  
Airway Reactivity ◽  
Pharmacological Modulation ◽  
Activation Mechanisms ◽  
Cross Bridges

Shen, X., M. F. Wu, R. S. Tepper, and S. J. Gunst. Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation. J. Appl. Physiol. 83(3): 739–745, 1997.—Stretch and retraction of the airways caused by changes in lung volume may play an important role in regulating airway reactivity. We studied the effects of different pharmacological stimuli on airway smooth muscle to determine whether the muscle behavior during length oscillation can be modulated pharmacologically and to evaluate the role of different activation mechanisms in determining its behavior during the oscillation. Active force decreased below the static isometric force during the shortening phase of length oscillation, resulting in an overall depression of force during the length oscillation cycle. This pattern of response was unaffected by the contractile stimulus or level of activation, suggesting that it was caused by a mechanism that is independent of the level of activation of cross bridges. The normalized area of the length-force hysteresis loop (hysteresivity) differed depending on the stimulus used for contraction. Effects of different stimuli on hysteresivity were not correlated with their effects on isotonic shortening velocity or isometric force, suggesting that the pharmacological modulation of the behavior of airway smooth muscle during length oscillation at these amplitudes cannot be accounted for by the effects on the cross-bridge cycling rate.

Invited Review: Do inflammatory mediators influence the contribution of airway smooth muscle contraction to airway hyperresponsiveness in asthma?

2003 ◽  
Vol 95 (2) ◽  
pp. 844-853 ◽  
Author(s):  
Darren J. Fernandes ◽  
Richard W. Mitchell ◽  
Oren Lakser ◽  
Maria Dowell ◽  
Alastair G. Stewart ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Inflammatory Mediators ◽  
Airway Hyperresponsiveness ◽  
Molecular Mechanisms ◽  
Normal Subjects ◽  
Smooth Muscle Contraction ◽  
Deep Inspiration ◽  
Contractile Apparatus ◽  
Muscle Shortening

It is now accepted that a host of cytokines, chemokines, growth factors, and other inflammatory mediators contributes to the development of nonspecific airway hyperresponsiveness in asthma. Yet, relatively little is known about how inflammatory mediators might promote airway structural remodeling or about the molecular mechanisms by which they might exaggerate smooth muscle shortening as observed in asthmatic airways. Taking a deep inspiration, which provides relief of bronchodilation in normal subjects, is less effective in asthmatic subjects, and some have speculated that this deficiency stems directly from an abnormality of airway smooth muscle and results in airway hyperresponsiveness to constrictor agonists. Here, we consider some of the mechanisms by which inflammatory mediators might acutely or chronically induce changes in the contractile apparatus that in turn might contribute to hyperresponsive airways in asthma.

Silver nanoparticles Induce Anti-Proliferative Effects on Airway Smooth Muscle Cells. Role of Nitric Oxide and Muscarinic Receptor Signaling Pathway

2013 ◽  
Vol 65 ◽  
pp. S104
Author(s):  
Manuel Alejandro Ramirez-Lee ◽  
Hector Rosas-Hernandez ◽  
Samuel Salazar-Garcia ◽  
Jose Manuel Gutiérrez-Hernández ◽  
Ricardo Espinosa- Tanguma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Silver Nanoparticles ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Receptor Signaling Pathway

Mechanism of partial adaptation in airway smooth muscle after a step change in length

2007 ◽  
Vol 103 (2) ◽  
pp. 569-577 ◽  
Author(s):  
Farah Ali ◽  
Leslie Chin ◽  
Peter D. Paré ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Intermediate State ◽  
Ultrastructural Changes ◽  
Myosin Filament ◽  
Shortening Velocity ◽  
Myosin Filaments ◽  
Partial Adaptation ◽  
Static Conditions

The phenomenon of length adaptation in airway smooth muscle (ASM) is well documented; however, the underlying mechanism is less clear. Evidence to date suggests that the adaptation involves reassembly of contractile filaments, leading to reconfiguration of the actin filament lattice and polymerization or depolymerization of the myosin filaments within the lattice. The time courses for these events are unknown. To gain insights into the adaptation process, we examined ASM mechanical properties and ultrastructural changes during adaptation. Step changes in length were applied to isolated bundles of ASM cells; changes in force, shortening velocity, and myosin filament mass were then quantified. A greater decrease in force was found following an acute decrease in length, compared with that of an acute increase in length. A decrease in myosin filament mass was also found with an acute decrease in length. The shortening velocity measured immediately after the length change was the same as that measured after the muscle had fully adapted to the new length. These observations can be explained by a model in which partial adaptation of the muscle leads to an intermediate state in which reconfiguration of the myofilament lattice occurred rapidly, followed by a relatively slow process of polymerization of myosin filaments within the lattice. The partially adapted intermediate state is perhaps more physiologically relevant than the fully adapted state seen under static conditions, and it simulates a more realistic behavior for ASM in vivo.

scholarly journals Mast cells are associated with exacerbations and eosinophilia in children with severe asthma

2016 ◽  
Vol 48 (5) ◽  
pp. 1320-1328 ◽  
Author(s):  
Guillaume Lezmi ◽  
Louise Galmiche-Rolland ◽  
Sabine Rioux ◽  
Francis Jaubert ◽  
Isabelle Tillie-Leblond ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mast Cells ◽  
Severe Asthma ◽  
Airway Smooth Muscle ◽  
Eosinophilic Inflammation ◽  
Symptomatic Group ◽  
Mucosal Mast Cells ◽  
Bronchial Biopsies ◽  
Positive Correlations

The role of mast cells in the pathogenesis of childhood asthma is poorly understood. We aimed to estimate the implication of airway mucosal mast cells in severe asthma and their relationship with clinical, functional, inflammatory and remodelling parameters.Bronchial biopsies were performed in 36 children (5–18 years) with severe asthma: 24 had frequent severe exacerbations and/or daily symptoms in the previous year (symptomatic group), and 12 had few symptoms and a persistent obstructive pattern (paucisymptomatic group). Nine children without asthma were included as control subjects. We assessed mast cells in the submucosa and airway smooth muscle using c-kit antibodies and in the entire biopsy area using Giemsa.The number of submucosal mast cells was higher in the symptomatic group than in the paucisymptomatic group (p=0.02). The number of submucosal mast cells correlated with the number of severe exacerbations (p=0.02, r=0.37). There were positive correlations between the number of submucosal mast cells (p<0.01, r=0.44), airway smooth muscle mast cells (p=0.02, r= 0.40), mast cells stained by Giemsa (p<0.01, r=0.44) and submucosal eosinophils.Mast cells are associated with severe exacerbations and submucosal eosinophilic inflammation in children with severe asthma.

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