scholarly journals A Brief History of Airway Smooth Muscle’s Role in Airway Hyperresponsiveness

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
C. D. Pascoe ◽  
L. Wang ◽  
H. T. Syyong ◽  
P. D. Paré
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Plastic Behavior ◽  
Phenotypic Changes ◽  
History Of Research ◽  
History Of ◽  
Cardiac Muscles ◽  
Precise Role

A link between airway smooth muscle (ASM) and airway hyperresponsiveness (AHR) in asthma was first postulated in the midnineteenth century, and the suspected link has garnered ever increasing interest over the years. AHR is characterized by excessive narrowing of airways in response to nonspecific stimuli, and it is the ASM that drives this narrowing. The stimuli that can be used to demonstrate AHR vary widely, as do the potential mechanisms by which phenotypic changes in ASM or nonmuscle factors can contribute to AHR. In this paper, we review the history of research on airway smooth muscle’s role in airway hyperresponsiveness. This research has ranged from analyzing the quantity of ASM in the airways to testing for alterations in the plastic behavior of smooth muscle, which distinguishes it from skeletal and cardiac muscles. This long history of research and the continued interest in this topic mean that the precise role of ASM in airway responsiveness remains elusive, which makes it a pertinent topic for this collection of articles.

LTD4 induces hyperresponsiveness to histamine in bovine airway smooth muscle: role of SR-ATPase Ca2+ pump and tyrosine kinase

2005 ◽  
Vol 288 (1) ◽  
pp. L84-L92 ◽  
Author(s):  
Verónica Carbajal ◽  
Mario H. Vargas ◽  
Edgar Flores-Soto ◽  
Erasmo Martínez-Cordero ◽  
Blanca Bazán-Perkins ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Tyrosine Kinase ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Response Curve ◽  
Cyclopiazonic Acid ◽  
Extracellular Signal ◽  
Intracellular Ca ◽  
Concentration Response Curve

Airway hyperresponsiveness is a key feature of asthma, but its mechanisms remain poorly understood. Leukotriene D4 (LTD4) is one of the few molecules capable of producing airway hyperresponsiveness. In this study, LTD4, but not leukotriene C4 (LTC4), produced a leftward displacement of the concentration-response curve to histamine in bovine airway smooth muscle strips. Neither LTC4 nor LTD4 modified the concentration-response curve to carbachol. In simultaneous measurements of intracellular Ca2+ ([Ca2+]i) and contraction, histamine or carbachol produced a transient Ca2+ peak followed by a plateau, along with a contraction. LTD4 increased the histamine-induced transient Ca2+ peak and contraction but did not modify responses to carbachol. Enhanced responses to histamine induced by LTD4 were not modified by staurosporine or chelerythrine but were abolished by genistein. Western blot showed that carbachol, but not histamine, caused intense phosphorylation of extracellular signal-regulated kinase 1/2 and that LTD4 significantly enhanced the phosphorylation induced by histamine, but not by carbachol. L-type Ca2+ channel participation in the hyperresponsiveness to histamine was discarded because LTD4 did not modify the [Ca2+]i changes induced by KCl. In tracheal myocytes, LTD4 enhanced the transient Ca2+ peak induced by histamine (but not by carbachol) and the sarcoplasmic reticulum (SR) Ca2+ refilling. Genistein abolished this last LTD4 effect. Partial blockade of the SR-ATPase Ca2+ pump with cyclopiazonic acid reduced the Ca2+ transient peak induced by histamine but not by carbachol. These results suggested that LTD4 induces hyperresponsiveness to histamine through activation of the tyrosine kinase pathway and an increasing SR-ATPase Ca2+ pump activity. L-type Ca2+ channels seemed not to be involved in this phenomenon.

Mechanisms of airway smooth muscle relaxation during maturation

2005 ◽  
Vol 83 (10) ◽  
pp. 833-840 ◽  
Author(s):  
Lu Wang ◽  
Thomas M Murphy ◽  
Pasquale Chitano
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Muscle Relaxation ◽  
Electrical Field Stimulation ◽  
Airway Responsiveness ◽  
Smooth Muscle Relaxation ◽  
Asthma Prevalence ◽  
Spontaneous Relaxation

Greater airway responsiveness in healthy juveniles is considered a factor in the higher asthma prevalence at a young age compared with adults. We have developed a guinea pig maturational model that utilizes tracheal strips from 1-week-, 3-week-, and 3-month-old guinea pigs to study the role of airway smooth muscle (ASM) in juvenile airway hyperresponsiveness. Because a reduced ability of ASM to spontaneously relax may contribute to airway hyperresponsiveness by maintaining bronchospasm and thus high airway resistance, we have employed this model to study ASM spontaneous relaxation during electrical field stimulation (EFS). Since relaxation during EFS had been neither described nor quantified during maturation, we developed new indices that allowed an appropriate comparison of the relaxing response from strips of different age animals. Using these indices we found that, whereas strips from adult animals relax to a level of tension similar to that found in the absence of stimulation, this ability to spontaneously relax is essentially absent in trachealis from infant animals. These results confirmed that maturation of ASM relaxation may play a role in juvenile airway hyperresponsiveness and that our maturational model is suitable to study the mechanisms regulating spontaneous relaxation in physiological conditions. We investigated the role of prostanoids in ASM relaxation and showed that cyclooxygenase inhibition increases relaxation in infant ASM to levels similar to adults. These results suggest that prostanoids regulate the ability of ASM to spontaneously relax, i.e., they reduce relaxation. We have produced preliminary data suggesting a maturational change in the level of prostanoids. Moreover, the possible action of acetylcholinesterase on maturation of ASM relaxation is discussed here on the basis of a preliminary study. We suggest that impairment of ASM relaxation likely contributes to increased airway responsiveness.Key words: acetylcholinesterase, airway responsiveness, asthma, ontogenesis, prostanoids.

Adrenomedullin insufficiency increases allergen-induced airway hyperresponsiveness in mice

2007 ◽  
Vol 102 (6) ◽  
pp. 2361-2368 ◽  
Author(s):  
Hiroshi Yamamoto ◽  
Takahide Nagase ◽  
Takayuki Shindo ◽  
Shinji Teramoto ◽  
Tomoko Aoki-Nagase ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Airway Responsiveness ◽  
Mutant Mice ◽  
Wild Type ◽  
T Helper 1 ◽  
Littermate Control

Adrenomedullin (ADM), a newly identified vasodilating peptide, is reported to be expressed in lungs and have a bronchodilating effect. We hypothesized whether ADM could be involved in the pathogenesis of bronchial asthma. We examined the role of ADM in airway responsiveness using heterozygous ADM-deficient mice ( AM+/−) and their littermate control ( AM+/+). Here, we show that airway responsiveness is enhanced in ADM mutant mice after sensitization and challenge with ovalbumin (OVA). The immunoreactive ADM level in the lung tissue after methacholine challenge was significantly greater in the wild-type mice than that in the mutant. However, the impairment of ADM gene function did not affect immunoglobulins (OVA-specific IgE and IgG1), T helper 1 and 2 cytokines, and leukotrenes. Thus the conventional mechanism of allergen-induced airway responsiveness is not relevant to this model. Furthermore, morphometric analysis revealed that eosinophilia and airway hypersecretion were similarly found in both the OVA-treated ADM mutant mice and the OVA-treated wild-type mice. On the other hand, the area of the airway smooth muscle layer of the OVA-treated mutant mice was significantly greater than that of the OVA-treated wild-type mice. These results suggest that ADM gene disruption may be associated with airway smooth muscle hyperplasia as well as enhanced airway hyperresponsiveness. ADM mutant mice might provide novel insights to study the pathophysiological role of ADM in vivo.

Ozone-induced airway hyperresponsiveness: roles of ROCK isoforms

2015 ◽  
Vol 309 (12) ◽  
pp. L1394-L1397 ◽  
Author(s):  
James A. Lambert ◽  
Weifeng Song
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Rho Kinase ◽  
Smooth Muscle Contraction ◽  
Wild Type ◽  
Epithelial Injury ◽  
Robust Evidence

Acute ozone (O3) inhalation has been shown to cause airway and pulmonary epithelial injury with accompanying inflammation responses. Robust evidence exists that O3 induces airway hyperresponsiveness (AHR) in humans and in animal models. Several pathways exist that culminate in airway smooth muscle contraction, but the mechanism(s) by which O3 elicits AHR are unclear. Here, we review the recent report by Kasahara et al. (Kasahara DI, Mathews JA, Park CY, Cho Y, Hunt G, Wurmbrand AP, Liao JK, Shore SA. Am J Physiol Lung Cell Mol Physiol 309: L736–L746, 2015.) describing the role of two Rho kinase (ROCK) isoforms in O3-induced AHR utilizing a murine haploinsufficiency model. Compared with wild-type (WT) mice, the authors report that ROCK1+/− and ROCK2+/− mice exhibited significantly reduced AHR following acute exposure to O3. Additionally, WT mice treated with fasudil, an FDA-approved ROCK1/2 inhibitor, recapitulated reduction in AHR as seen in ROCK haplotypes. It was suggested that, although the two ROCK isoforms are both induced by Rho, they have different mechanisms by which they mediate O3-induced AHR: ROCK1 via hyaluronan signaling vs. ROCK2 acting downstream of inflammation at the level of airway smooth muscle contraction. These observations provide an important framework to develop novel ROCK-targeting therapies for acute O3-induced AHR.

Interleukin-9 influences chemokine release in airway smooth muscle: role of ERK

2003 ◽  
Vol 284 (6) ◽  
pp. L1093-L1102 ◽  
Author(s):  
Simonetta Baraldo ◽  
Deborah S. Faffe ◽  
Paul E. Moore ◽  
Timothy Whitehead ◽  
Matthew McKenna ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Human Airway Smooth Muscle ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Tnf Α ◽  
Cox 2 ◽  
Interleukin 9

Interleukin (IL)-9 is a pleiotropic cytokine that has been proposed as a candidate gene for asthma. As IL-9 expression is correlated with airway hyperresponsiveness in animals, we examined the effects of IL-9 on cultured human airway smooth muscle (HASM) cells. IL-9 alone had no effect on IL-8 release, but at concentrations of ≥30 ng/ml, IL-9 significantly increased IL-8 release induced by TNF-α. IL-9 increased phosphorylation of extracellular signal-regulated protein kinase (ERK, p42 and p44) in a concentration- and time-dependent fashion, and U-0126 (10 μM), which inhibits ERK phosphorylation, abolished the synergism between TNF-α and IL-9 on IL-8 release. IL-9 alone had no effect on eotaxin release into HASM cell supernatants but at concentrations of ≥10 ng/ml caused an ∼50% increase in release of eotaxin evoked by IL-13 (10 ng/ml). U-0126 blocked the synergism between IL-9 and IL-13 on eotaxin release. IL-9 had no effect on cyclooxygenase-2 (COX-2) expression or PGE2release and did not augment the COX-2 expression that was induced by IL-1β. Our results indicate that airway smooth muscle is a target for IL-9 and that IL-9 amplifies the potential for these cells to recruit eosinophils and neutrophils into the airways by a mechanism involving ERK.

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.

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
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