Experimental progressive emphysema in BALB/cJ mice as a model for chronic alveolar destruction in humans

Abstract

Limjunyawong N, Craig JM, Lagassé HA, Scott AL, Mitzner W. Experimental progressive emphysema in BALB/cJ mice as a model for chronic alveolar destruction in humans.

Elimination of p19ARF‐expressing cells protects against pulmonary emphysema in mice

“…As alveolar fibroblasts are the major p19 ARF ‐expressing cells in the lung (Figure 1f; Hashimoto et al, 2016), these cells likely affected the expression of MMP‐12 and TIMP‐2 cell nonautonomously through SASP. Consistent with previous findings (Limjunyawong et al, 2015; Ueno et al, 2015), the expression of these genes was mostly diminished after 3 weeks, and DT also had a minor effect on these genes at this time point (Figures 5b and S5b). Collectively, these results suggest that the presence of p19 ARF ‐expressing cells in lung tissues facilitates the accumulation of inflammatory cells during the early phase of a PPE challenge, which promotes the development of emphysema‐associated pathologies.…”

“…Although a significant change was observed in lung morphology and function 3 weeks after the administration of PPE (Figures 2 and 3), no significant difference was found in the number or composition of inflammatory cells in BALF among PPE‐ and/or DT‐treated samples at this time point (Figure S3). This result was expected because a single shot of PPE only has temporal effects on BALF cells in the C57BL/6J strain (Limjunyawong, Craig, Lagassé, Scott, & Mitzner, 2015; Ueno et al, 2015). Therefore, we analyzed BALF cells at an earlier time point after the administration of PPE.…”

Immune-mediated inflammation in the pathogenesis of emphysema: insights from mouse models

“…We have reported a simple approach that circumvents the problems with measurement of diffusing capacity in mice (Fallica, et al, 2011, Limjunyawong, et al, 2015c). This procedure results in a very reproducible measurement, that is sensitive to a host of pathologic changes in the lung phenotype, including being able to follow the emphysematous changes over time(Limjunyawong, et al, 2015a). …”

“…Immediately after administration of elastase, the population of lung-resident macrophages decreases, but they quickly recover. Macrophages, eosinophils, and lymphocytes (both CD4 and CD8 T cells) remain elevated for weeks in the post-elastase lung and the elevation of these cells is associated with rapid and worsening lung damage that can be visualized histologically (Limjunyawong, Craig, Lagasse, Scott and Mitzner, 2015a) and measured by decrements in lung function (Figure 2 and Figure 3). At later times, there are increased numbers of CD4+ and CD8+ T cells with significant enlargement of airspaces within 21 days (Kurimoto, Miyahara, Kanehiro, Waseda, Taniguchi, Ikeda, Koga, Nishimori, Tanimoto, Kataoka, Iwakura, Gelfand and Tanimoto, 2013) (Figure 2).…”

Animal Models of Chronic Obstructive Pulmonary Disease Exacerbations: A Review of the Current Status

“…However, as in CS models, these effects are dependent on several factors, including strain; enzyme dose at each instillation; and number of elastase challenges (Figure 2). Limjunyawong et al recently reported that BALB/C mice are more sensitive than C57BL/6J to elastase injury, as demonstrated by significantly greater mortality, weight loss, decline in lung function, and loss of alveolar tissue [89]. Regarding dose and number of elastase challenges, Lüthje et al demonstrated that mice subjected to five elastase administrations with a 1-week interval between them developed not only a more severe alveolar destruction, but also systemic associated with systemic effects [36].…”