Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice

• DOI: 10.1073/pnas.100448997
• Publication Date: 2002-07-26T14:38:21Z
• Authors: Susan E. Wert; Mitsuhiro Yoshida; Ann Marie LeVine; Machiko Ikegami; Tracy Jones; Gary F. Ross; James H. Fisher; Thomas R. Korfhagen; Jeffrey A. Whitsett
• Keywords: Pathogenesis; MMP9; Immunostaining

Targeted ablation of the surfactant protein D (SP-D) gene caused chronic inflammation, emphysema, and fibrosis in lungs SP-D (−/−) mice. Although lung morphology was unperturbed during first 2 weeks life, airspace enlargement observed by 3 progressed with advancing age. Inflammation consisted hypertrophic alveolar macrophages peribronchiolar-perivascular monocytic infiltrates. These abnormalities were associated increased activity matrix metalloproteinases, MMP2 MMP9, immunostaining for MMP9 MMP12 macrophages. Hydrogen peroxide production isolated also significantly (10-fold). plays a critical role suppression macrophage activation, which may contribute to pathogenesis inflammation emphysema.