Hickling T P, Bright H, Wing K, Gower D, Martin S L, Sim R B, Malhotra R
GlaxoWellcome Medicines Research Centre, Stevenage, GB.
Eur J Immunol. 1999 Nov;29(11):3478-84. doi: 10.1002/(SICI)1521-4141(199911)29:11<3478::AID-IMMU3478>3.0.CO;2-W.
The pulmonary collectin, lung surfactant protein D (SP-D), plays a role in host defense mediated by the interaction of surface carbohydrates of inhaled pathogens with the lectin domains of SP-D. Respiratory syncytial virus (RSV), the most important viral pathogen of neonates and infants, encodes a highly glycosylated attachment protein, G. Binding studies were performed with G protein from RSV (human, A2 strain) and both native and recombinant human SP-D. The effect of recombinant trimeric SP-D lectin domains (rSP-D) on the interaction between RSV and host cells was determined by two methods: an infectivity study with monolayers of Hep-2C cells and in vivo infections in BALB/c mice. These studies show that full-length and recombinant SP-D bind to RSV G protein in a concentration-dependent manner. Both EDTA and mannan inhibited binding of full-length SP-D. These results indicate that binding occurs via the carbohydrate recognition domain of the SP-D. The recombinant SP-D inhibited RSV infectivity in cell culture in a dose-dependent manner, giving 100% inhibition of replication. Intranasal administration of recombinant SP-D to RSV-infected mice inhibited replication of the virus in the lungs, reducing levels of lung virus by 80%. These results suggest that SP-D plays a major role in clearing RSV from the lungs.
肺凝集素——肺表面活性蛋白D（SP-D），在宿主防御中发挥作用，该防御由吸入病原体的表面碳水化合物与SP-D的凝集素结构域相互作用介导。呼吸道合胞病毒（RSV）是新生儿和婴儿最重要的病毒病原体，它编码一种高度糖基化的附着蛋白G。利用来自RSV（人源，A2株）的G蛋白以及天然和重组人SP-D进行了结合研究。通过两种方法确定重组三聚体SP-D凝集素结构域（rSP-D）对RSV与宿主细胞之间相互作用的影响：对Hep-2C细胞单层进行感染性研究以及在BALB/c小鼠体内进行感染实验。这些研究表明全长和重组SP-D以浓度依赖的方式与RSV G蛋白结合。EDTA和甘露聚糖均抑制全长SP-D的结合。这些结果表明结合是通过SP-D的碳水化合物识别结构域发生的。重组SP-D在细胞培养中以剂量依赖的方式抑制RSV感染性，对病毒复制的抑制率达100%。对感染RSV的小鼠鼻内给药重组SP-D可抑制病毒在肺中的复制，使肺内病毒水平降低80%。这些结果表明SP-D在从肺中清除RSV方面发挥主要作用。
