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
      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%).

      PMIScience.com is operated by Philip Morris International for the purpose of publishing and disseminating scientific information about Philip Morris International’s efforts in support of its smoke-free product portfolio. This site is a global site for use by scientists, the public health and regulatory communities, and other stakeholders with an interest in tobacco policy. The purpose of this site is not advertising or marketing, nor is it directed at any specific market. It is not intended for use by consumers. New tobacco products sold in the United States are subject to FDA regulation; therefore the content of this site is not intended to make, and nor should it be construed as making, any product related claims in the United States without proper FDA authorization. ​
      ​
      Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.