A ‘Good’ muscle in a ‘Bad’ environment: The importance of airway smooth muscle force adaptation to airway hyperresponsiveness

2011 ◽  
Vol 179 (2-3) ◽  
pp. 269-275 ◽  
Author(s):  
Ynuk Bossé ◽  
David G. Chapman ◽  
Peter D. Paré ◽  
Gregory G. King ◽  
Cheryl M. Salome
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Muscle Force

Does the length dependency of airway smooth muscle force contribute to airway hyperresponsiveness?

2013 ◽  
Vol 115 (9) ◽  
pp. 1304-1315 ◽  
Author(s):  
Audrey Lee-Gosselin ◽  
Chris D. Pascoe ◽  
Christian Couture ◽  
Peter D. Paré ◽  
Ynuk Bossé
Keyword(s):  
Smooth Muscle ◽  
Computational Model ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Muscle Force ◽  
Morphological Data ◽  
Airway Wall ◽  
Airway Walls ◽  
Computational Analyses ◽  
Human Bronchi

Airway wall remodeling and lung hyperinflation are two typical features of asthma that may alter the contractility of airway smooth muscle (ASM) by affecting its operating length. The aims of this study were as follows: 1) to describe in detail the “length dependency of ASM force” in response to different spasmogens; and 2) to predict, based on morphological data and a computational model, the consequence of this length dependency of ASM force on airway responsiveness in asthmatic subjects who have both remodeled airway walls and hyperinflated lungs. Ovine tracheal ASM strips and human bronchial rings were isolated and stimulated to contract in response to increasing concentrations of spasmogens at three different lengths. Ovine tracheal strips were more sensitive and generated greater force at longer lengths in response to acetylcholine (ACh) and K+. Equipotent concentrations of ACh were approximately a log less for ASM stretched by 30% and approximately a log more for ASM shortened by 30%. Similar results were observed in human bronchi in response to methacholine. Morphometric and computational analyses predicted that the ASM of asthmatic subjects may be elongated by 6.6–10.4% (depending on airway generation) due to remodeling and/or hyperinflation, which could increase ACh-induced force by 1.8–117.8% (depending on ASM length and ACh concentration) and enhance the increased resistance to airflow by 0.4–4,432.8%. In conclusion, elongation of ASM imposed by airway wall remodeling and/or hyperinflation may allow ASM to operate at a longer length and to consequently generate more force and respond to lower concentration of spasmogens. This phenomenon could contribute to airway hyperresponsiveness.

scholarly journals Altered CD38/Cyclic ADP-Ribose Signaling Contributes to the Asthmatic Phenotype

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Joseph A. Jude ◽  
Mythili Dileepan ◽  
Reynold A. Panettieri ◽  
Timothy F. Walseth ◽  
Mathur S. Kannan
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Intracellular Calcium ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Map Kinases ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Cd38 Expression ◽  
Cyclic Adp Ribose

CD38 is a transmembrane glycoprotein expressed in airway smooth muscle cells. The enzymatic activity of CD38 generates cyclic ADP-ribose from β-NAD. Cyclic ADP-ribose mobilizes intracellular calcium during activation of airway smooth muscle cells by G-protein-coupled receptors through activation of ryanodine receptor channels in the sarcoplasmic reticulum. Inflammatory cytokines that are implicated in asthma upregulate CD38 expression and increase the calcium responses to contractile agonists in airway smooth muscle cells. The augmented intracellular calcium responses following cytokine exposure of airway smooth muscle cells are inhibited by an antagonist of cyclic ADP-ribose. Airway smooth muscle cells from CD38 knockout mice exhibit attenuated intracellular calcium responses to agonists, and these mice have reduced airway response to inhaled methacholine. CD38 also contributes to airway hyperresponsiveness as shown in mouse models of allergen or cytokine-induced inflammatory airway disease. In airway smooth muscle cells obtained from asthmatics, the cytokine-induced CD38 expression is significantly enhanced compared to expression in cells from nonasthmatics. This differential induction of CD38 expression in asthmatic airway smooth muscle cells stems from increased activation of MAP kinases and transcription through NF-κB, and altered post-transcriptional regulation through microRNAs. We propose that increased capacity for CD38 signaling in airway smooth muscle in asthma contributes to airway hyperresponsiveness.

scholarly journals Rhinovirus C15 Induces Airway Hyperresponsiveness via Calcium Mobilization in Airway Smooth Muscle

2020 ◽  
Vol 62 (3) ◽  
pp. 310-318 ◽  
Author(s):  
Vishal Parikh ◽  
Jacqueline Scala ◽  
Riva Patel ◽  
Corinne Corbi ◽  
Dennis Lo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Calcium Mobilization

Endothelin-1 contributes to antigen-induced airway hyperresponsiveness

1995 ◽  
Vol 79 (3) ◽  
pp. 700-705 ◽  
Author(s):  
K. Noguchi ◽  
K. Ishikawa ◽  
M. Yano ◽  
A. Ahmed ◽  
A. Cortes ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Intravenous Infusion ◽  
Airway Hyperresponsiveness ◽  
Antigen Challenge ◽  
Late Response ◽  
Eta Receptor ◽  
Airway Responses ◽  
Eta Receptor Antagonist ◽  
Stimulation Of

Endothelin A (ETA)-receptors mediate ET-1 contractions of ovine airway smooth muscle. Therefore, the ETA-receptor antagonist, BQ-123, was used to test the hypothesis that ET-1 contributes to antigen-induced airway responses in sheep allergic to Ascaris suum. We first established the protective effect of BQ-123 by demonstrating that BQ-123 given as an aerosol (0.3 or 1.0 mg/kg in 3 ml buffer) or by continuous intravenous infusion (100 micrograms.kg-1.min-1) significantly blocked the bronchoconstriction to aerosolized ET-1 (0.2–200 micrograms/ml). To determine whether ET-1 contributed to antigen-induced airway responses, BQ-123 was given either as an intravenous infusion (100 micrograms.kg-1.min-1) beginning 30 min before and continuing for 8 h after antigen challenge or as an aerosol (1 mg/kg in 3 ml buffer) 30 min before and 4, 8, and 24 h after antigen challenge. Neither treatment with intravenous infusion nor aerosolized BQ-123 blocked the immediate antigen-induced bronchoconstriction, but both treatments significantly reduced the late response (approximately 50%). The treatments with aerosolized BQ-123 also blocked the antigen-induced airway hyperresponsiveness to inhaled carbachol seen 24 h after challenge. Subsequently, we found that sheep developed airway hyperresponsiveness to inhaled carbachol at 4 and 24 h after ET-1 challenge, an effect that was blocked by aerosolized BQ-123. We conclude that in allergic sheep 1) aerosolized ET-1 causes bronchoconstriction, in part, by stimulation of ETA-receptors, 2) ET-1 is released in the airways after antigen challenge, and 3) this peptide contributes to the severity of the allergic responses, probably by increasing airway smooth muscle responsiveness.

Inflammation and cell-cell interactions in airway hyperresponsiveness

1991 ◽  
Vol 260 (4) ◽  
pp. L189-L206 ◽  
Author(s):  
A. R. Leff ◽  
K. J. Hamann ◽  
C. D. Wegner
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Difficult Problem ◽  
Experimental Models ◽  
Cytotoxic Effects ◽  
Epithelial Secretion ◽  
Eosinophil Granule ◽  
Conducting Airways ◽  
Reactive Airways

Airway hyperresponsiveness results from the conversion of normally reactive airways to a state of augmented responsiveness to constrictor stimuli. Although the mechanism accounting for the induction of airway hyperresponsiveness remains elusive, recent investigations have suggested that inflammation may be a sine qua non for human asthma. Numerous experimental models have demonstrated the necessity of circulating granulocytes as mediators of augmented bronchoconstriction during immune challenge. It is not known how granulocytes are targeted for selective migration to the conducting airways of the lung during hyperresponsive states; however, recent evidence implicates the upregulation of granulocyte adhesion molecules on both the endothelial and epithelial surfaces of the airway. There is evidence that during migration diapedesis, granulocytes interact with epithelial and endothelial cells to produce regionally secreted mediators that upregulate the responsiveness of adjacent airway smooth muscle and/or cause lumenal edema, thus augmenting the effect of constrictor stimuli. Most evidence suggests that the eosinophil is the most important granulocyte in these responses and that eosinophilic infiltration and activation may account for the unique, spasmodic, and cyclic nature of hyperreactive airways. The molecular biology of the eosinophil granule proteins has characterized four distinct substances, each of which exerts potential cytotoxic effects on airway epithelium by different mechanism. In addition, at least one of these proteins, the major basic protein, appears to cause direct, noncytotoxic stimulation of epithelial secretion that upregulates nonspecifically the response of airway smooth muscle to contractile stimuli. The recognition of inflammation as the essential component to airway hyperresponsiveness provides a fresh approach to a difficult problem and suggests a host of novel therapies for human asthma.

Interleukin-1β-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway

2002 ◽  
Vol 283 (5) ◽  
pp. L909-L917 ◽  
Author(s):  
Z.-X. Wu ◽  
B. E. Satterfield ◽  
J. S. Fedan ◽  
R. D. Dey
Keyword(s):  
Smooth Muscle ◽  
Substance P ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Sensory Nerves ◽  
Tracheal Smooth Muscle ◽  
Fiber Density ◽  
Smooth Muscle Contractility ◽  
Neurokinin 1

Interleukin (IL)-1β causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1β. Ferrets were instilled intratracheally with IL-1β (0.3 μg/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and substance P (SP) expression in tracheal neurons were assessed. Tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) and smooth muscle contractions to electric field stimulation (EFS) both increased after IL-1β. The IL-1β-induced AHR was maintained in tracheal segments cultured for 24 h, a procedure that depletes SP from sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the IL-1β-induced hyperreactivity to ACh and MCh and to EFS in cultured tracheal segments. SP-containing neurons in longitudinal trunk, SP innervation of superficial muscular plexus neurons, and SP nerve fiber density in tracheal smooth muscle all increased after treatment with IL-1β. These results show that IL-1β-enhanced cholinergic airway smooth muscle contractile responses are mediated by the actions of SP released from intrinsic airway neurons.

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