RT Journal Article
SR Electronic
T1 A novel non-human primate model of cigarette smoke-induced chronic obstructive pulmonary disease
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P864
VO 44
IS Suppl 58
A1 Francesca Polverino
A1 Melanie Doyle-Eisele
A1 Jacob McDonald
A1 Julie Wilder
A1 Emer Kelly
A1 Joe Mauderly
A1 Victor Pinto-Plata
A1 Miguel Divo
A1 Bartolome Celli
A1 Yohannes Tesfaigzi
A1 Caroline Ann Owen
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P864.abstract
AB Background:Commonly used small animal models have limitations for identifying new therapeutic targets or biomarkers for COPD. Herein, we assessed the utility of cigarette smoke(CS)-exposed non-human primates(NHPs) as a novel animal model of COPD.Methods:16 NHPs from the breeding colony at LRRI were exposed to air or CS for 12 weeks. Bronchoalveolar lavage (BAL) and pulmonary function tests were performed at baseline and after 4 and 12 weeks. Lung samples were obtained at euthanasia. We quantified:1)inflammation by counting leukocytes in BAL samples and lung sections; 2)lung oxidative stress measuring thiobarbituric acid reactive substances(TBARS) in lungs; 3)alveolar septal cell apoptosis using TUNEL staining; 4)airspace enlargement using morphometry; 5)airway mucus metaplasia using PAS and MUC5AC stainings; and 6)deposition of extracellular matrix(ECM) using Trichrome staining.Results: Compared to controls, CS-exposed NHPs showed a 20% reduction in FVC0.1. Moreover, they developed: 1)lung inflammation with 2-4 fold increase in BAL macrophages and PMNs; 2)4-fold increases in TBARS levels; 3)alveolar septal cell apoptosis; 4)mucus metaplasia in large and small airways; 5)fibrosis around small airways and vessels and 6)T and B lymphocyte follicles in the lungs. 12 weeks of CS-exposure were not sufficient to develop significant emphysema.Conclusions:NHPs show reduced lung function and a progressive lung inflammatory response to CS, together with other pathological processes similar to those occurring in human cigarette smokers. This novel animal model of COPD can safely undergo longitudinal sampling, and could be useful for testing novel biomarkers or new therapeutics for COPD.