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The Journal of allergy and clinical immunology2004; 114(2 Suppl); S2-S17; doi: 10.1016/j.jaci.2004.04.039

Proliferative aspects of airway smooth muscle.

Abstract: Increased airway smooth muscle (ASM) mass is perhaps the most important component of the airway wall remodeling process in asthma. Known mediators of ASM proliferation in cell culture models fall into 2 categories: those that activate receptors with intrinsic receptor tyrosine kinase activity and those that have their effects through receptors linked to heterotrimeric guanosine triphosphate-binding proteins. The major candidate signaling pathways activated by ASM mitogens are those dependent on extracellular signal-regulated kinase and phosphoinositide 3'-kinase. Increases in ASM mass may also involve ASM migration, and in culture, the key signaling mechanisms have been identified as the p38 mitogen-activated protein kinase and the p21-activated kinase 1 pathways. New evidence from an in vivo rat model indicates that primed CD4(+) T cells are sufficient to trigger ASM and epithelial remodeling after allergen challenge. Hyperplasia has been observed in an equine model of asthma and may account for the increase in ASM mass. Reduction in the rate of apoptosis may also play a role. beta(2)-Adrenergic receptor agonists and glucocorticoids have antiproliferative activity against a broad spectrum of mitogens, although it has become apparent that mitogens are differentially sensitive. Culture of ASM on collagen type I has been shown to enhance proliferative activity and prevent the inhibitory effect of glucocorticoids, whereas beta(2)-agonists are minimally affected. There is no evidence that long-acting beta(2)-agonists are more effective than short-acting agonists, but persistent stimulation of the beta(2)-adrenergic receptor probably helps suppress growth responses. The maximum response of fluticasone propionate against thrombin-induced proliferation is increased when it is combined with salmeterol.
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Publication Date: 2004-08-17 PubMed ID: 15309015DOI: 10.1016/j.jaci.2004.04.039Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article delves into the increased mass of airway smooth muscle (ASM) in asthma, its causes, and mechanisms, as well as studying the effects of certain drugs on this proliferation. It uses both in vivo and in vitro studies on different models, including equine and rat, for a comprehensive understanding.

Understanding the Growth of Airway Smooth Muscle

  • The study starts by establishing that the increase in airway smooth muscle (ASM) mass is a significant feature in asthma’s airway wall remodeling process.
  • Two categories of mediators are identified as responsible for the ASM proliferation. One category activates receptors coupled with intrinsic tyrosine kinase activity, and the other has its effects via receptors associated with heterotrimeric guanosine triphosphate-binding proteins.
  • The key signaling pathways activated by these ASM growth triggers are primarily the extracellular signal-regulated kinase and the phosphoinositide 3′-kinase.
  • Moreover, the research implies that ASM mass expansion might not just be about cell multiplication but also migration, with p38 mitogen-activated protein kinase and the p21-activated kinase 1 pathways being the major signaling mechanisms.

Empirical Evidence from Animal Models

  • They introduce findings from an in vivo rat model that showed primed CD4(+) T cells can induce ASM and epithelial remodeling after allergen exposure.
  • Hyperplasia or an abnormal increase in volume of a tissue or organ due to the increased rate of cell replication was also found in an equine model of asthma, which corroborates with the increased ASM mass.
  • Furthermore, it proposes that a decreased apoptosis or cell death rate might contribute to the increase in airway smooth muscle.

Effects of Drugs on ASM

  • The research then discusses the effects of drugs, specifically beta(2)-adrenergic receptor agonists (drugs that relax muscles of the airways, increasing airflow) and glucocorticoids (used for their anti-inflammatory effects), on the proliferation of ASM.
  • Both types of drugs showed antiproliferative activity against a range of mitogens, but the sensitivity of mitogens varied.
  • The study also found that cultivating ASM on type I collagen intensified the proliferative activity and hindered the suppressive effect of glucocorticoids. In contrast, beta(2)-agonists effects were only marginally impacted.
  • Interestingly, there was no evidence suggesting that long-acting beta(2)-agonists are more effective than short-acting agonists, but persistent stimulation of the beta(2)-adrenergic receptor might assist in growth response suppression.
  • Lastly, the maximum response of fluticasone propionate, a corticosteroid, against thrombin-induced proliferation was increased when combined with salmeterol, a long-acting beta2-adrenergic receptor agonist.

Cite This Article

APA
Hirst SJ, Martin JG, Bonacci JV, Chan V, Fixman ED, Hamid QA, Herszberg B, Lavoie JP, McVicker CG, Moir LM, Nguyen TT, Peng Q, Ramos-Barbón D, Stewart AG. (2004). Proliferative aspects of airway smooth muscle. J Allergy Clin Immunol, 114(2 Suppl), S2-S17. https://doi.org/10.1016/j.jaci.2004.04.039

Publication

The Journal of allergy and clinical immunology
ISSN: 0091-6749
NlmUniqueID: 1275002
Country: United States
Language: English
Volume: 114
Issue: 2 Suppl
Pages: S2-S17

Researcher Affiliations

Hirst, Stuart J
  • Department of Asthma, Allergy and Respiratory Science, Guy's, King's and St. Thomas' School of Medicine, Guy's Hospital Campus, King's College London, United Kingdom. stuart.hirst@kcl.ac.uk
Martin, James G
    Bonacci, John V
      Chan, Vivien
        Fixman, Elizabeth D
          Hamid, Qutayba A
            Herszberg, Berenice
              Lavoie, Jean-Pierre
                McVicker, Clare G
                  Moir, Lyn M
                    Nguyen, Trang T-B
                      Peng, Qi
                        Ramos-Barbón, David
                          Stewart, Alastair G

                            MeSH Terms

                            • Adrenergic beta-Agonists / pharmacology
                            • Allergens / immunology
                            • Animals
                            • Bronchi / cytology
                            • Cell Division
                            • Cell Movement
                            • Glucocorticoids / pharmacology
                            • Humans
                            • Hyperplasia
                            • Hypertrophy
                            • Mitogen-Activated Protein Kinases / physiology
                            • Myocytes, Smooth Muscle / physiology
                            • Signal Transduction
                            • T-Lymphocytes / physiology
                            • Trachea / cytology

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