PT  - JOURNAL ARTICLE
AU  - Nadja Baumgartl
AU  - Holger Garn
AU  - Agnieszka Turowska
AU  - Norbert Weissmann
TI  - Autoimmune induction of a COPD-like inflammatory phenotype in mice
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - P615
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/P615.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/P615.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - Chronic obstructive pulmonary disease (COPD) is a life-threatening lung disease associated with chronic inflammation. Tobacco smoke exposure has been identified as most common cause, but the pathogenetic mechanisms are still poorly understood. Recent studies suggest that autoimmune mechanisms, probably directed against degraded components of the extracellular matrix, contribute to induction and/or perpetuation of the disease-underlying inflammatory processes. Therefore, we hypothesized that experimental induction of an autoimmune response to elastin may result in a COPD-like inflammatory phenotype in the lungs of mice.To test this hypothesis, we initially immunized C57Bl/6 mice to bovine elastin (69.8 % homology to mouse elastin) and applied several booster immunizations using a mixture of bovine and rat elastin (86.3 % homology). We analyzed the development of mouse elastin-specific autoantibodies and characterized the induction of an inflammatory response in the lungs. Over time, increasing titers of anti-mouse-elastin IgG antibodies were detected indicating a successful induction of an autoimmune response. Additionally, increased lymphocyte levels were observed in the bronchoalveolar lavage and in lung homogenates. Histologically, peripheral inflammatory foci comparable to those observed in lungs of COPD patients as well as peribronchial inflammation processes were observed.To evaluate the potential role of Th1 cells and their transcription factor T-bet Tbet-/- mice will be tested in this model. Moreover, the model will be combined with continuous cigarette-smoke exposure to analyze the role of smoke-induced extracellular matrix degradation on the perpetuation of already established autoimmune processes.