Sorensen Grith L, Madsen Jens, Kejling Karin, Tornoe Ida, Nielsen Ole, Townsend Paul, Poulain Francis, Nielsen Claus H, Reid Kenneth B M, Hawgood Samuel, Falk Erling, Holmskov Uffe
Medical Biotechnology Center, University of Southern Denmark, Winsloewparken 25,3, 5000 Odense C, Denmark.
Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2286-94. doi: 10.1152/ajpheart.01105.2005. Epub 2005 Dec 30.
Surfactant protein D (SP-D) is an important innate immune defense molecule that mediates clearance of pathogens and modulates the inflammatory response. Moreover, SP-D is involved in lipid homeostasis, and pulmonary accumulation of phospholipids has previously been observed in SP-D-deficient (Spd-/-) mice. Atherogenesis involves both inflammation and lipid deposition, and we investigated the role of SP-D in the development of atherosclerosis. SP-D synthesis was localized to vascular endothelial cells. Atherosclerotic lesion areas were 5.6-fold smaller in the aortic roots in Spd-/- mice compared with wild-type C57BL/6N mice on an atherogenic diet. HDL cholesterol (HDL-C) was significantly elevated in Spd-/- mice. Treatment of Spd-/- mice with a recombinant fragment of human SP-D resulted in decreases of HDL-C (21%) as well as total cholesterol (26%), and LDL cholesterol (28%). Plasma TNF-alpha was reduced in Spd-/- mice (45% difference). SP-D was proatherogenic in the mouse model used. The effect is likely to be due to the observed disturbances of plasma lipid metabolism and alteration of the inflammatory process, which underlie the reduced susceptibility to atherosclerosis in Spd-/- mice.
表面活性蛋白D（SP-D）是一种重要的天然免疫防御分子，可介导病原体的清除并调节炎症反应。此外，SP-D参与脂质稳态，此前在SP-D缺陷（Spd-/-）小鼠中观察到磷脂在肺部的蓄积。动脉粥样硬化的发生涉及炎症和脂质沉积，我们研究了SP-D在动脉粥样硬化发展中的作用。SP-D的合成定位于血管内皮细胞。在致动脉粥样硬化饮食条件下，Spd-/-小鼠主动脉根部的动脉粥样硬化病变面积比野生型C57BL/6N小鼠小5.6倍。Spd-/-小鼠的高密度脂蛋白胆固醇（HDL-C）显著升高。用人SP-D的重组片段治疗Spd-/-小鼠导致HDL-C降低（21%）以及总胆固醇降低（26%）和低密度脂蛋白胆固醇降低（28%）。Spd-/-小鼠血浆肿瘤坏死因子-α降低（差异45%）。在所使用的小鼠模型中，SP-D具有促动脉粥样硬化作用。这种作用可能是由于观察到的血浆脂质代谢紊乱和炎症过程改变，这些是Spd-/-小鼠对动脉粥样硬化易感性降低的基础。
