Emphysema, one of the major components of
chronic obstructive pulmonary disease (
COPD), is characterized by the progressive and irreversible loss of alveolar lung tissue. Even though >80% of
COPD cases are associated with cigarette smoking, only a relatively small proportion of smokers develop
emphysema, suggesting a potential role for genetic factors in determining individual susceptibility to
emphysema. Although strain-dependent effects have been shown in animal models of
emphysema, the molecular basis underlying this intrinsic susceptibility is not fully understood. In this present study, we investigated
emphysema development using the
elastase-induced experimental
emphysema model in two commonly used mouse strains, C57BL/6J and BALB/cJ. The results demonstrate that mice with different genetic backgrounds show disparate susceptibility to the development of
emphysema. BALB/cJ mice were found to be much more sensitive than C57BL/6J to
elastase injury in both a dose-dependent and time-dependent manner, as measured by significantly higher mortality, greater
body weight loss, greater decline in lung function, and a greater loss of alveolar tissue. The more susceptible BALB/cJ strain also showed the persistence of inflammatory cells in the lung, especially macrophages and lymphocytes. A comparative gene expression analysis following
elastase-induced injury showed BALB/cJ mice had elevated levels of il17A
mRNA and a number of classically (M1) and alternatively (M2) activated macrophage genes, whereas the C57BL/6J mice demonstrated augmented levels of
interferon-γ. These findings suggest a possible role for these cellular and molecular mediators in modulating the severity of
emphysema and highlight the possibility that they might contribute to the heterogeneity observed in clinical
emphysema outcomes.