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

Targeted ablation of the surfactant protein D (SP-D) gene caused chronic in flammation, emphysema, and fibrosis in the lungs of SP-D (-/-) mice. Althou gh lung morphology was unperturbed during the first 2 weeks of life, airspa ce enlargement was observed by 3 weeks and progressed with advancing age. I nflammation consisted of hypertrophic alveolar macrophages and peribronchio lar-perivascular monocytic infiltrates. These abnormalities were associated with increased activity of the matrix metalloproteinases, MMP2 and MMP9, a nd immunostaining for MMP9 and MMP12 in alveolar macrophages. Hydrogen pero xide production by isolated alveolar macrophages also was increased signifi cantly (10-fold). SP-D plays a critical role in the suppression of alveolar macrophage activation, which may contribute to the pathogenesis of chronic inflammation and emphysema.