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Published in: Lung 2/2017

01-04-2017

Bronchoconstriction Induces Structural and Functional Airway Alterations in Non-sensitized Rats

Authors: Mehdi Eslami-Behroozi, Saeed Pazhoohan, Ehsan Aref, Leila Zare, Mohammad Javan, Sohrab Hajizadeh, Mohammad Reza Raoufy

Published in: Lung | Issue 2/2017

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Abstract

The impact of mechanical forces on pathogenesis of airway remodeling and the functional consequences in asthma remains to be fully established. In the present study, we investigated the effect of repeated bronchoconstriction induced by methacholine (MCh) on airway remodeling and airway hyperresponsiveness (AHR) in rats with or without sensitization to an external allergen. We provide evidence that repeated bronchoconstriction, using MCh, alone induces airway inflammation and remodeling as well as AHR in non-allergen-sensitized rats. Also, we found that the airways are structurally and functionally altered by bronchoconstriction induced by either allergen or MCh in allergen-sensitized animals. This finding provides a new animal model for the development of airway remodeling and AHR in mammals and can be used for studying the complex reciprocal relationship between bronchoconstriction and airway inflammation. Further studies on presented animal models are required to clarify the exact mechanisms underlying airway remodeling due to bronchoconstriction and the functional consequences.
Literature
1.
go back to reference Fahy JV (2001) Remodeling of the airway epithelium in asthma. Am J Respir Crit Care Med 164:S46–S51CrossRefPubMed Fahy JV (2001) Remodeling of the airway epithelium in asthma. Am J Respir Crit Care Med 164:S46–S51CrossRefPubMed
3.
go back to reference Humbles AA, Lloyd CM, McMillan SJ et al (2004) A critical role for eosinophils in allergic airways remodeling. Science 305:1776–1779CrossRefPubMed Humbles AA, Lloyd CM, McMillan SJ et al (2004) A critical role for eosinophils in allergic airways remodeling. Science 305:1776–1779CrossRefPubMed
5.
go back to reference Crimi E, Spanevello A, Neri M et al (1998) Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. Am J Respir Crit Care Med 157:4–9CrossRefPubMed Crimi E, Spanevello A, Neri M et al (1998) Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. Am J Respir Crit Care Med 157:4–9CrossRefPubMed
6.
go back to reference Anderson GP (2008) Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 372:1107–1119CrossRefPubMed Anderson GP (2008) Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 372:1107–1119CrossRefPubMed
7.
9.
10.
go back to reference Swartz MA, Tschumperlin DJ, Kamm RD et al (2001) Mechanical stress is communicated between different cell types to elicit matrix remodeling. Proc Natl Acad Sci USA 98:6180–6185CrossRefPubMedPubMedCentral Swartz MA, Tschumperlin DJ, Kamm RD et al (2001) Mechanical stress is communicated between different cell types to elicit matrix remodeling. Proc Natl Acad Sci USA 98:6180–6185CrossRefPubMedPubMedCentral
11.
go back to reference Wahl M, Eddinger TJ, Hai CM (2004) Sinusoidal length oscillation- and receptor-mediated mRNA expression of myosin isoforms and alpha-SM actin in airway smooth muscle. Am J Physiol Cell Physiol 287:C1697–C1708CrossRefPubMed Wahl M, Eddinger TJ, Hai CM (2004) Sinusoidal length oscillation- and receptor-mediated mRNA expression of myosin isoforms and alpha-SM actin in airway smooth muscle. Am J Physiol Cell Physiol 287:C1697–C1708CrossRefPubMed
12.
go back to reference Grainge CL, Lau LC, Ward JA et al (2011) Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med 364:2006–2015CrossRefPubMed Grainge CL, Lau LC, Ward JA et al (2011) Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med 364:2006–2015CrossRefPubMed
13.
go back to reference Grainge C, Dennison P, Lau L et al (2014) Asthmatic and normal respiratory epithelial cells respond differently to mechanical apical stress. Am J Respir Crit Care Med 190:477–480CrossRefPubMedPubMedCentral Grainge C, Dennison P, Lau L et al (2014) Asthmatic and normal respiratory epithelial cells respond differently to mechanical apical stress. Am J Respir Crit Care Med 190:477–480CrossRefPubMedPubMedCentral
14.
go back to reference Sapienza S, Du T, Eidelman DH et al (1991) Structural changes in the airways of sensitized Brown Norway rats after antigen challenge. Am Rev Respir Dis 144:423–427CrossRefPubMed Sapienza S, Du T, Eidelman DH et al (1991) Structural changes in the airways of sensitized Brown Norway rats after antigen challenge. Am Rev Respir Dis 144:423–427CrossRefPubMed
15.
go back to reference Szema AM, Hamidi SA, Lyubsky S et al (2006) Mice lacking the VIP gene show airway hyperresponsiveness and airway inflammation, partially reversible by VIP. Am J Physiol Lung Cell Mol Physiol 291:L880–L886CrossRefPubMed Szema AM, Hamidi SA, Lyubsky S et al (2006) Mice lacking the VIP gene show airway hyperresponsiveness and airway inflammation, partially reversible by VIP. Am J Physiol Lung Cell Mol Physiol 291:L880–L886CrossRefPubMed
16.
go back to reference Ma JY, Medicherla S, Kerr I et al (2008) Selective p38α mitogen-activated protein kinase inhibitor attenuates lung inflammation and fibrosis in IL-13 transgenic mouse model of asthma. J Asthma Allergy 1:31–44CrossRefPubMedPubMedCentral Ma JY, Medicherla S, Kerr I et al (2008) Selective p38α mitogen-activated protein kinase inhibitor attenuates lung inflammation and fibrosis in IL-13 transgenic mouse model of asthma. J Asthma Allergy 1:31–44CrossRefPubMedPubMedCentral
17.
go back to reference Dehghan S, Hesaraki M, Soleimani M et al (2016) Oct4 transcription factor in conjunction with valproic acid accelerates myelin repair in demyelinated optic chiasm in mice. Neuroscience 318:178–189CrossRefPubMed Dehghan S, Hesaraki M, Soleimani M et al (2016) Oct4 transcription factor in conjunction with valproic acid accelerates myelin repair in demyelinated optic chiasm in mice. Neuroscience 318:178–189CrossRefPubMed
18.
go back to reference Gosens R, Grainge C (2015) Bronchoconstriction and airway biology: potential impact and therapeutic opportunities. Chest 147:798–803CrossRefPubMed Gosens R, Grainge C (2015) Bronchoconstriction and airway biology: potential impact and therapeutic opportunities. Chest 147:798–803CrossRefPubMed
19.
go back to reference Evans MJ, Fanucchi MV, Plopper CG et al (2010) Postnatal development of the lamina reticularis in primate airways. Anat Rec 293:947–954CrossRef Evans MJ, Fanucchi MV, Plopper CG et al (2010) Postnatal development of the lamina reticularis in primate airways. Anat Rec 293:947–954CrossRef
21.
go back to reference Pera T, Zuidhof A, Valadas J et al (2011) Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD. Eur Respir J 38:789–796CrossRefPubMed Pera T, Zuidhof A, Valadas J et al (2011) Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD. Eur Respir J 38:789–796CrossRefPubMed
22.
go back to reference Kistemaker LE, Bos ST, Mudde WM et al (2014) Muscarinic M3 receptors contribute to allergen-induced airway remodeling in mice. Am J Respir Cell Mol Biol 50:690–698CrossRefPubMed Kistemaker LE, Bos ST, Mudde WM et al (2014) Muscarinic M3 receptors contribute to allergen-induced airway remodeling in mice. Am J Respir Cell Mol Biol 50:690–698CrossRefPubMed
23.
go back to reference Undem BJ, Nassenstein C (2009) Airway nerves and dyspnea associated with inflammatory airway disease. Respir Physiol Neurobiol 167:36–44CrossRefPubMed Undem BJ, Nassenstein C (2009) Airway nerves and dyspnea associated with inflammatory airway disease. Respir Physiol Neurobiol 167:36–44CrossRefPubMed
24.
go back to reference Niimi A, Torrego A, Nicholson AG et al (2005) Nature of airway inflammation and remodeling in chronic cough. J Allergy Clin Immunol 116:565–570CrossRefPubMed Niimi A, Torrego A, Nicholson AG et al (2005) Nature of airway inflammation and remodeling in chronic cough. J Allergy Clin Immunol 116:565–570CrossRefPubMed
25.
go back to reference Berry M, Morgan A, Shaw DE et al (2007) Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax 62:1043–1049CrossRefPubMedPubMedCentral Berry M, Morgan A, Shaw DE et al (2007) Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax 62:1043–1049CrossRefPubMedPubMedCentral
Metadata
Title
Bronchoconstriction Induces Structural and Functional Airway Alterations in Non-sensitized Rats
Authors
Mehdi Eslami-Behroozi
Saeed Pazhoohan
Ehsan Aref
Leila Zare
Mohammad Javan
Sohrab Hajizadeh
Mohammad Reza Raoufy
Publication date
01-04-2017
Publisher
Springer US
Published in
Lung / Issue 2/2017
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-016-9970-4

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