Korfhagen T R, Sheftelyevich V, Burhans M S, Bruno M D, Ross G F, Wert S E, Stahlman M T, Jobe A H, Ikegami M, Whitsett J A, Fisher J H
Division of Pulmonary Biology, Department of Pediatrics, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
J Biol Chem. 1998 Oct 23;273(43):28438-43. doi: 10.1074/jbc.273.43.28438.
Surfactant protein D (SP-D) is a 43-kDa member of the collectin family of collagenous lectin domain-containing proteins that is expressed in epithelial cells of the lung. The SP-D gene was targeted by homologous recombination in embryonic stem cells that were used to produce SP-D (+/-) and SP-D (-/-) mice. Both SP-D (-/-) and SP-D (+/-) mice survived normally in the perinatal and postnatal periods. Whereas no abnormalities were observed in SP-D (+/-) mice, alveolar and tissue phosphatidylcholine pool sizes were markedly increased in SP-D (-/-) mice. Increased numbers of large foamy alveolar macrophages and enlarged alveoli were also observed in SP-D (-/-) mice. Phospholipid composition was unaltered in SP-D (-/-) mice, but surfactant morphology was abnormal, consisting of dense phospholipid membranous arrays with decreased tubular myelin. The pulmonary lipoidosis in the SP-D (-/-) mice was not associated with accumulation of surfactant proteins B or C, or their mRNAs, distinguishing the disorder from alveolar proteinosis syndromes. Surfactant protein A mRNA was reduced and, SP-A protein appeared to be reduced in SP-D (-/-) compared with wild type mice. Targeting of the mouse SP-D gene caused accumulation of surfactant lipid and altered phospholipid structures, demonstrating a previously unsuspected role for SP-D in surfactant lipid homeostasis in vivo.
表面活性蛋白D（SP-D）是包含胶原凝集素结构域的蛋白的凝集素家族中一个43千道尔顿的成员，在肺上皮细胞中表达。SP-D基因在胚胎干细胞中通过同源重组被靶向，这些胚胎干细胞被用于培育SP-D（+/-）和SP-D（-/-）小鼠。SP-D（-/-）和SP-D（+/-）小鼠在围产期和出生后均正常存活。虽然在SP-D（+/-）小鼠中未观察到异常，但SP-D（-/-）小鼠的肺泡和组织磷脂酰胆碱池大小显著增加。在SP-D（-/-）小鼠中还观察到大量大泡沫肺泡巨噬细胞数量增加以及肺泡增大。SP-D（-/-）小鼠的磷脂组成未改变，但表面活性剂形态异常，由致密的磷脂膜阵列组成，管状髓鞘减少。SP-D（-/-）小鼠的肺类脂沉积症与表面活性蛋白B或C及其mRNA的积累无关，这将该病症与肺泡蛋白沉积症综合征区分开来。与野生型小鼠相比，SP-D（-/-）小鼠中表面活性蛋白A mRNA减少，且SP-A蛋白似乎也减少。小鼠SP-D基因的靶向导致表面活性剂脂质积累并改变磷脂结构，表明SP-D在体内表面活性剂脂质稳态中具有先前未被怀疑的作用。
