A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis

Beckett, EL; Stevens, RL; Jarnicki, AG; Kim, RY; Hanish, I; Hansbro, NG; Deane, A; Keely, S; Horvat, JC; Yang, M; Oliver, BG; Van Rooijen, N; Inman, MD; Adachi, R; Soberman, RJ; Hamadi, S; Wark, PA; Foster, PS; Hansbro, PM

A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis

Beckett, EL Stevens, RL Jarnicki, AG Kim, RY

Hanish, I Hansbro, NG Deane, A Keely, S Horvat, JC Yang, M Oliver, BG

Van Rooijen, N Inman, MD Adachi, R Soberman, RJ Hamadi, S Wark, PA Foster, PS Hansbro, PM

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Publication Type:: Journal Article
Citation:: Journal of Allergy and Clinical Immunology, 2013, 131 (3)
Issue Date:: 2013-01-01

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Field	Value	Language
dc.contributor.author	Beckett, EL	en_US
dc.contributor.author	Stevens, RL	en_US
dc.contributor.author	Jarnicki, AG	en_US
dc.contributor.author	Kim, RY https://orcid.org/0000-0002-8709-5270	en_US
dc.contributor.author	Hanish, I	en_US
dc.contributor.author	Hansbro, NG	en_US
dc.contributor.author	Deane, A	en_US
dc.contributor.author	Keely, S	en_US
dc.contributor.author	Horvat, JC	en_US
dc.contributor.author	Yang, M	en_US
dc.contributor.author	Oliver, BG https://orcid.org/0000-0002-7122-9262	en_US
dc.contributor.author	Van Rooijen, N	en_US
dc.contributor.author	Inman, MD	en_US
dc.contributor.author	Adachi, R	en_US
dc.contributor.author	Soberman, RJ	en_US
dc.contributor.author	Hamadi, S	en_US
dc.contributor.author	Wark, PA	en_US
dc.contributor.author	Foster, PS	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.date.available	2012-11-27	en_US
dc.date.issued	2013-01-01	en_US
dc.identifier.citation	Journal of Allergy and Clinical Immunology, 2013, 131 (3)	en_US
dc.identifier.issn	0091-6749	en_US
dc.identifier.uri	http://hdl.handle.net/10453/88970
dc.description.abstract	Background: Cigarette smoke-induced chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory disorder of the lung. The development of effective therapies for COPD has been hampered by the lack of an animal model that mimics the human disease in a short timeframe. Objectives: We sought to create an early-onset mouse model of cigarette smoke-induced COPD that develops the hallmark features of the human condition in a short time-frame. We also sought to use this model to better understand pathogenesis and the roles of macrophages and mast cells (MCs) in patients with COPD. Methods: Tightly controlled amounts of cigarette smoke were delivered to the airways of mice, and the development of the pathologic features of COPD was assessed. The roles of macrophages and MC tryptase in pathogenesis were evaluated by using depletion and in vitro studies and MC protease 6-deficient mice. Results: After just 8 weeks of smoke exposure, wild-type mice had chronic inflammation, mucus hypersecretion, airway remodeling, emphysema, and reduced lung function. These characteristic features of COPD were glucocorticoid resistant and did not spontaneously resolve. Systemic effects on skeletal muscle and the heart and increased susceptibility to respiratory tract infections also were observed. Macrophages and tryptase-expressing MCs were required for the development of COPD. Recombinant MC tryptase induced proinflammatory responses from cultured macrophages. Conclusion: A short-term mouse model of cigarette smoke-induced COPD was developed in which the characteristic features of the disease were induced more rapidly than in existing models. The model can be used to better understand COPD pathogenesis, and we show a requirement for macrophages and tryptase-expressing MCs. © 2013 American Academy of Allergy, Asthma & Immunology.	en_US
dc.relation.ispartof	Journal of Allergy and Clinical Immunology	en_US
dc.relation.isbasedon	10.1016/j.jaci.2012.11.053	en_US
dc.subject.classification	Allergy	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Mast Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Tobacco	en_US
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Respiratory Function Tests	en_US
dc.subject.mesh	Smoke	en_US
dc.subject.mesh	Tryptases	en_US
dc.subject.mesh	Airway Remodeling	en_US
dc.title	A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	131	en_US
utslib.for	1107 Immunology	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	131	en_US

Abstract:

Background: Cigarette smoke-induced chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory disorder of the lung. The development of effective therapies for COPD has been hampered by the lack of an animal model that mimics the human disease in a short timeframe. Objectives: We sought to create an early-onset mouse model of cigarette smoke-induced COPD that develops the hallmark features of the human condition in a short time-frame. We also sought to use this model to better understand pathogenesis and the roles of macrophages and mast cells (MCs) in patients with COPD. Methods: Tightly controlled amounts of cigarette smoke were delivered to the airways of mice, and the development of the pathologic features of COPD was assessed. The roles of macrophages and MC tryptase in pathogenesis were evaluated by using depletion and in vitro studies and MC protease 6-deficient mice. Results: After just 8 weeks of smoke exposure, wild-type mice had chronic inflammation, mucus hypersecretion, airway remodeling, emphysema, and reduced lung function. These characteristic features of COPD were glucocorticoid resistant and did not spontaneously resolve. Systemic effects on skeletal muscle and the heart and increased susceptibility to respiratory tract infections also were observed. Macrophages and tryptase-expressing MCs were required for the development of COPD. Recombinant MC tryptase induced proinflammatory responses from cultured macrophages. Conclusion: A short-term mouse model of cigarette smoke-induced COPD was developed in which the characteristic features of the disease were induced more rapidly than in existing models. The model can be used to better understand COPD pathogenesis, and we show a requirement for macrophages and tryptase-expressing MCs. © 2013 American Academy of Allergy, Asthma & Immunology.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/88970