Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice
Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice
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DOI：
10.1073/pnas.100448997
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发表时间：
2000-05-23
影响因子：
11.1
通讯作者：
Whitsett, JA
中科院分区：
文献类型：
--
作者：
Wert, SE;Yoshida, M;Whitsett, JA
表面活性蛋白D（SP-D）基因的靶向消融导致SP-D（-/-）小鼠肺部慢性炎症、肺气肿和纤维化。虽然肺形态在出生后的前2周内未受影响，但在3周内观察到了肺空间扩大，并随着年龄的增长而进展。炎症由肥大的肺泡巨噬细胞和细支气管-血管周围单核细胞浸润组成。这些异常与肺泡巨噬细胞中基质金属蛋白酶MMP 2和MMP 9的活性增加以及MMP 9和MMP 12的免疫染色有关。离体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。
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.