Posters

    Characterization of Strain A Mice as a Potential Model for Lung Emphysema

    Van Miert, E.; Friedrichs, B.; Weiler, H.; Pype, J.; Peck, M.; Vanscheeuwijck, P.

    Conference date
    Nov 9, 2008
    Conference name
    American College of Toxicology (ACT) 2008
    Link to more information
    Topic
    Summary

    Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD). A relevant animal model of COPD is needed to evaluate products with potentially reduced risk. The objective of this study was to assess the suitability of the strain a mouse as a model for cigarette-smoke-induced lung emphysema. Female A/J mice, 6 months old, were exposed to diluted mainstream smoke from the reference cigarette 2R4F for 2, 3, or 4 h/day, 5 days/week for 5 months. The mean smoke concentration throughout the study was 735 µg total particulate matter/l. After 5 months, pronounced lung inflammation was observed, as evidenced by increased numbers of neutrophils (37-fold) and lymphocytes (6-fold) in bronchoalveolar lavage fluid (BALF). Alveolar macrophages showed an increased activation status, as indicated by increased expression levels of CD11B (414-fold) and CD86 (10-fold). A large number of pro-inflammatory mediators in BALF were increased, especially neutrophil and monocyte chemoattractants (e.g., MIP2: 4-fold and MCP1: 94-fold). The most pronounced change in BALF was observed for IgA (149-fold), which suggests a humoral response. Lung inflammation was accompanied by increased levels of MMP9 (45-fold) and TIMP-1 (at least 6-fold) in BALF. No significant inflammation-related changes were observed in the bronchial lymph nodes or in serum. Pulmonary function measurements indicated an increased tissue elastance (up to +33%) and a decreased Paomax (up to -38%), which are indicative of structural changes in the lung. Morphometric measurements showed an increased mean chord length at the highest dose (+32%).

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