title: Automated measurement of pulmonary emphysema and small airway remodeling in cigarette smoke-exposed mice.
abstract: COPD is projected to be the third most common cause of mortality world-wide by 2020((1)). Animal models of COPD are used to identify molecules that contribute to the disease process and to test the efficacy of novel therapies for COPD. Researchers use a number of models of COPD employing different species including rodents, guinea-pigs, rabbits, and dogs((2)). However, the most widely-used model is that in which mice are exposed to cigarette smoke. Mice are an especially useful species in which to model COPD because their genome can readily be manipulated to generate animals that are either deficient in, or over-express individual proteins. Studies of gene-targeted mice that have been exposed to cigarette smoke have provided valuable information about the contributions of individual molecules to different lung pathologies in COPD((3-5)). Most studies have focused on pathways involved in emphysema development which contributes to the airflow obstruction that is characteristic of COPD. However, small airway fibrosis also contributes significantly to airflow obstruction in human COPD patients((6)), but much less is known about the pathogenesis of this lesion in smoke-exposed animals. To address this knowledge gap, this protocol quantifies both emphysema development and small airway fibrosis in smoke-exposed mice. This protocol exposes mice to CS using a whole-body exposure technique, then measures respiratory mechanics in the mice, inflates the lungs of mice to a standard pressure, and fixes the lungs in formalin. The researcher then stains the lung sections with either Gill's stain to measure the mean alveolar chord length (as a readout of emphysema severity) or Masson's trichrome stain to measure deposition of extracellular matrix (ECM) proteins around small airways (as a readout of small airway fibrosis). Studies of the effects of molecular pathways on both of these lung pathologies will lead to a better understanding of the pathogenesis of COPD.
authors: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital - Harvard Medical School.
authors: Maria E
authors: ME
authors: Laucho-Contreras
authors: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital - Harvard Medical School.
authors: Katherine L
authors: KL
authors: Taylor
authors: Department of Respiratory Medicine, University of Cambridge - Addenbrooke's Hospital.
authors: Ravi
authors: R
authors: Mahadeva
authors: Lung Transplant Program, Brigham and Women's Hospital - Harvard Medical School.
authors: Steve S
authors: SS
authors: Boukedes
authors: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital - Harvard Medical School; COPD and IPF Programs, Lovelace Respiratory Research Institute; cowen1@partners.org.
authors: Caroline A
authors: CA
authors: Owen
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D008168:Lung / Q000473:pathology; D051379:Mice; D011650:Pulmonary Alveoli / Q000473:pathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000473:pathology*; D012907:Smoking / Q000473:pathology*
references: Am J Respir Crit Care Med. 2012 Jan 1;185(1):34-43
references: 21997333
references: Inhal Toxicol. 2006 Oct;18(11):911-8
references: 16864409
references: Mod Pathol. 2003 Jan;16(1):1-7
references: 12527706
references: Am J Respir Cell Mol Biol. 2009 Apr;40(4):482-90
references: 18931327
references: Am J Pathol. 2008 Oct;173(4):949-61
references: 18772344
references: Thorax. 1962 Dec;17(4):320-28
references: 25269161
references: Exp Pathol. 1989;37(1-4):194-7
references: 2637153
references: Lab Anim. 2011 Apr;45(2):81-9
references: 21357700
references: Am Rev Respir Dis. 1989 Feb;139(2):308-12
references: 2913883
references: Am J Respir Crit Care Med. 2006 Dec 15;174(12):1327-34
references: 17008639
references: Am Rev Respir Dis. 1985 May;131(5):764-9
references: 4003921
references: Am J Physiol Lung Cell Mol Physiol. 2008 Jul;295(1):L1-15
references: 18456796
references: J Vis Exp. 2013;(75):e50172
references: 23711876
references: Am J Respir Crit Care Med. 2004 Nov 1;170(9):974-80
references: 15282203
references: Nat Med. 1995 Mar;1(3):215-20
references: 7585036
references: N Engl J Med. 2004 Jun 24;350(26):2645-53
references: 15215480
references: Front Physiol. 2013 Jun 12;4:132
references: 23781205
references: FASEB J. 2013 Apr;27(4):1585-99
references: 23325319
references: J Clin Invest. 2014 Sep;124(9):3987-4003
references: 25083992
references: Science. 1997 Sep 26;277(5334):2002-4
references: 9302297
references: Am J Respir Cell Mol Biol. 2011 Dec;45(6):1111-5
references: 21685155
references: Clin Sci (Lond). 2014 Feb;126(4):253-65
references: 24144354
references: N Engl J Med. 2013 Aug 1;369(5):448-57
references: 23902484
references: Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15571-6
references: 20713693