Katja Fischer 1 , 2 , Jan-Moritz Doehn 1 , Christian Herr 3 , Carolin Lachner 2 , Annina Heinrich 2 , Olivia Kershaw 4 , Meike Voss 3 , Max H. Jacobson 5 , Achim D. Gruber 4 , Matthias Clauss 6 , Martin Witzenrath 1 , 7 , Robert Bals 3 , Birgitt Gutbier 1 , 7 , Hortense Slevogt 2 , *
In chronic obstructive pulmonary disease (COPD), acute exacerbations and emphysema development are characteristics for disease pathology. COPD is complicated by infectious exacerbations with acute worsening of respiratory symptoms with Moraxella catarrhalis as one of the most frequent pathogens. Although cigarette smoke (CS) is the primary risk factor, additional molecular mechanisms for emphysema development induced by bacterial infections are incompletely understood. We investigated the impact of M. catarrhalis on emphysema development in CS exposed mice and asked whether an additional infection would induce a solubilization of pro-apoptotic and pro-inflammatory endothelial monocyte-activating-protein-2 (EMAPII) to exert its activities in the pulmonary microvasculature and other parts of the lungs not exposed directly to CS.
Mice were exposed to smoke (6 or 9 months) and/or infected with M. catarrhalis. Lungs, bronchoalveolar lavage fluid (BALF), and plasma were analyzed.
CS exposure reduced ciliated area, caused rarefaction of the lungs, and induced apoptosis. EMAPII was increased independent of prior smoke exposure in BALF of infected mice. Importantly, acute M. catarrhalis infection increased release of matrixmetalloproteases-9 and -12, which are involved in emphysema development and comprise a mechanism of EMAPII release.
Our data suggest that acute M. catarrhalis infection represents an independent risk factor for emphysema development in smoke-exposed mice.