Structural Emphysema Does Not Correlate With Lung Compliance: Lessons From the Mouse Smoking Model

Abstract

The murine smoke-induced model produces histologic emphysema. The authors sought to assess whether the structural emphysema that occurred correlated with the development of compliance changes. The study exposed 2 strains of mice (CBA/J/J x C57BL/6J and A/J) to chronic cigarette smoke. Lung compliance and morphometry were measured. The smoking model generated significant emphysema in A/J mice in the absence of changes in compliance, lung matrix, or apoptosis. Importantly, there was no correlation between the emphysema measured by lung morphometry and pulmonary compliance. This lack of correlation suggests that the mechanisms involved in anatomic emphysema may be distinct from those that cause the loss of elastic recoil.

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

“…The number of Mac-3-positive cells in the lung sections (five random microscopic fields per lung section in three different sections) were counted manually under microscope with ϫ200 magnification and averaged. [27][28][29] Similarly, 8-OHdG was detected by immunohistochemistry in paraffin-embedded sections pretreated with 100 g⅐ml Ϫ1 ribonuclease A in PBS to inhibit nonspecific binding to RNA using a mouse monoclonal antibody (Oxis International Inc., Foster City, CA). The number of 8-OHdG-positive cells in the lung sections (three random microscopic fields per lung section in three different sections) was also counted manually in a blinded manner.…”

Second hand smoke and COPD: lessons from animal studies

“…Again, the AKR/J mice demonstrate smoke-induced increases in macrophages, PMNs, and T cells with a Th1 cytokine predominance; increased alveolar macrophages were also noted in the C57BL6/J and NZWLac/J mice (Foronjy et al, 2005). In vitro analysis of alveolar macrophages from susceptible (C57BL6/J) and resistant (ICR) strains demonstrates that alveolar macrophages from susceptible mice release increased proinflammatory cytokines and MMPs when exposed to cigarette smoke, and have a higher baseline production of reactive oxygen species as compared to those obtained from resistant mice (Vecchio et al, 2010).…”

“…The NZWLac/J mice did not develop any increase in mean linear intercept (11% decrease as compared to control mice) (Guerassimov et al, 2004). Furthermore, despite detectible, albeit modest, alterations in lung morphometry, there is not necessarily a correlation with alterations in lung mechanics (Guerassimov et al, 2004;Foronjy et al, 2005).…”

“…Chronic smoke exposure was also found to reduce antigen-specific T-cell proliferative response in pulmonary associated lymph nodes (Chang et al, 1990) as well as the phagocytic index of macrophages (Ortega et al, 1992). Although structural changes in the mouse lung occur after long-term smoke exposure, it is important to note that the changes in mice following chronic smoke exposure are still only mild as measured by mean linear intercept or lung compliance (Foronjy et al, 2005(Foronjy et al, , 2006Churg et al, 2008).…”

“…One of the most important considerations in smoke exposure studies is understanding that the development of emphysema in a chronic smoke exposure model, as measured by morphometry and lung compliance, is mouse strain dependent (Guerassimov et al, 2004;Foronjy et al, 2005). In a comprehensive study performed by Guerassimov and colleagues, NZWLac/J, C57BL6/J, A/J, SJ/L, and AKR/J strains underwent 6 months of cigarette smoke exposure.…”