García-Mouton Cristina, Hidalgo Alberto, Arroyo Raquel, Echaide Mercedes, Cruz Antonio, Pérez-Gil Jesús
Department of Biochemistry and Molecular Biology, Faculty of Biology, Research Institute "Hospital 12 de Octubre (imas12)," Complutense University, Madrid, Spain.
Front Bioeng Biotechnol. 2021 Jan 18;8:613276. doi: 10.3389/fbioe.2020.613276. eCollection 2020.
This work is focused on the potential use of pulmonary surfactant to deliver full-length recombinant human surfactant protein SP-D (rhSP-D) using the respiratory air-liquid interface as a shuttle. Surfactant protein D (SP-D) is a collectin protein present in the pulmonary surfactant (PS) system, involved in innate immune defense and surfactant homeostasis. It has been recently suggested as a potential therapeutic to alleviate inflammatory responses and lung diseases in preterm infants suffering from respiratory distress syndrome (RDS) or bronchopulmonary dysplasia (BPD). However, none of the current clinical surfactants used for surfactant replacement therapy (SRT) to treat RDS contain SP-D. The interaction of SP-D with surfactant components, the potential of PS as a respiratory drug delivery system and the possibility to produce recombinant versions of human SP-D, brings the possibility of delivering clinical surfactants supplemented with SP-D. Here, we used an setup that somehow emulates the respiratory air-liquid interface to explore this novel approach. It consists in two different compartments connected with a hydrated paper bridge forming a continuous interface. We firstly analyzed the adsorption and spreading of rhSP-D alone from one compartment to another over the air-liquid interface, observing low interfacial activity. Then, we studied the interfacial spreading of the protein co-administered with PS, both at different time periods or as a mixed formulation, and which oligomeric forms of rhSP-D better traveled associated with PS. The results presented here demonstrated that PS may transport rhSP-D long distances over air-liquid interfaces, either as a mixed formulation or separately in a close window time, opening the doors to empower the current clinical surfactants and SRT.
这项工作聚焦于利用肺表面活性剂，以呼吸气液界面作为载体来递送全长重组人表面活性蛋白SP-D（rhSP-D）。表面活性蛋白D（SP-D）是一种存在于肺表面活性剂（PS）系统中的凝集素蛋白，参与固有免疫防御和表面活性剂稳态。最近，它被认为是一种潜在的治疗方法，可缓解患有呼吸窘迫综合征（RDS）或支气管肺发育不良（BPD）的早产儿的炎症反应和肺部疾病。然而，目前用于治疗RDS的表面活性剂替代疗法（SRT）的临床表面活性剂中均不含SP-D。SP-D与表面活性剂成分的相互作用、PS作为呼吸药物递送系统的潜力以及生产重组人SP-D的可能性，带来了递送补充有SP-D的临床表面活性剂的可能性。在此，我们使用了一种以某种方式模拟呼吸气液界面的装置来探索这种新方法。它由两个不同的隔室组成，通过一个含水纸桥相连，形成一个连续的界面。我们首先分析了rhSP-D单独从一个隔室通过气液界面吸附并扩散到另一个隔室的情况，观察到其界面活性较低。然后，我们研究了与PS共同给药的蛋白质在不同时间段或作为混合制剂时的界面扩散情况，以及哪种rhSP-D寡聚体形式与PS结合时扩散得更好。此处呈现的结果表明，PS可以在气液界面上长距离运输rhSP-D，无论是作为混合制剂还是在相近的时间段内单独运输，这为增强当前的临床表面活性剂和SRT打开了大门。
