Wert S E, Yoshida M, LeVine A M, Ikegami M, Jones T, Ross G F, Fisher J H, Korfhagen T R, Whitsett J A
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
Proc Natl Acad Sci U S A. 2000 May 23;97(11):5972-7. doi: 10.1073/pnas.100448997.
Targeted ablation of the surfactant protein D (SP-D) gene caused chronic inflammation, emphysema, and fibrosis in the lungs of SP-D (-/-) mice. Although lung morphology was unperturbed during the first 2 weeks of life, airspace enlargement was observed by 3 weeks and progressed with advancing age. Inflammation consisted of hypertrophic alveolar macrophages and peribronchiolar-perivascular monocytic infiltrates. These abnormalities were associated with increased activity of the matrix metalloproteinases, MMP2 and MMP9, and immunostaining for MMP9 and MMP12 in alveolar macrophages. Hydrogen peroxide production by isolated alveolar macrophages also was increased significantly (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.
表面活性蛋白D（SP-D）基因的靶向消融导致SP-D（-/-）小鼠肺部出现慢性炎症、肺气肿和纤维化。虽然在出生后的前2周肺形态未受干扰，但在3周时观察到气腔扩大，并随着年龄增长而进展。炎症表现为肺泡巨噬细胞肥大和支气管周围-血管周围单核细胞浸润。这些异常与基质金属蛋白酶MMP2和MMP9的活性增加以及肺泡巨噬细胞中MMP9和MMP12的免疫染色有关。分离的肺泡巨噬细胞产生的过氧化氢也显著增加（10倍）。SP-D在抑制肺泡巨噬细胞活化中起关键作用，这可能有助于慢性炎症和肺气肿的发病机制。
