Department of Biochemistry and Molecular Biology, Faculty of Biology and Faculty of Chemistry, Complutense University, Madrid, Spain; Research Institute "Hospital 12 de Octubre (imas12)", Madrid, Spain.
Department of Biochemistry and Molecular Biology, Institute for Biotechnology and Biomedicine (BIOTECMED), University of Valencia, Valencia, Spain.
Biochim Biophys Acta Biomembr. 2021 Jun 1;1863(6):183572. doi: 10.1016/j.bbamem.2021.183572. Epub 2021 Feb 4.
Surfactant protein C (SP-C) is a protein present in the pulmonary surfactant system that is involved in the biophysical properties of this lipoprotein complex, but it also has a role in lung defense and homeostasis. In this article, we propose that the link between both functions could rely on the ability of SP-C to induce fragmentation of phospholipid membranes and generate small vesicles that serve as support to present different ligands to cells in the lungs. Our results using bimolecular fluorescence complementation and tunable resistive pulse sensing setups suggest that SP-C oligomerization could be the triggering event that causes membrane budding and nanovesiculation. As shown by fluorescence microscopy and flow cytometry, these vesicles are differentially assimilated by alveolar macrophages and alveolar type II cells, indicating distinct roles of these alveoli-resident cells in the processing of the SP-C- induced vesicles and their cargo. These results depict a more accurate picture of the mechanisms of this protein, which could be relevant for the comprehension of pulmonary pathologies and the development of new therapeutic approaches.
表面活性蛋白 C（SP-C）是肺表面活性物质系统中存在的一种蛋白，它参与该脂蛋白复合物的生物物理特性，但它在肺防御和稳态中也具有作用。在本文中，我们提出，这两种功能之间的联系可能依赖于 SP-C 诱导磷脂膜断裂和生成小泡的能力，这些小泡作为支持物，向肺部的细胞呈现不同的配体。我们使用双分子荧光互补和可调电阻脉冲感应装置的结果表明，SP-C 寡聚化可能是导致膜出芽和纳米囊泡形成的触发事件。如荧光显微镜和流式细胞术所示，这些小泡被肺泡巨噬细胞和肺泡 II 型细胞以不同的方式摄取，表明这些肺泡驻留细胞在处理 SP-C 诱导的小泡及其货物方面具有不同的作用。这些结果描绘了该蛋白机制的更准确图景，这对于理解肺部病理学和开发新的治疗方法可能具有重要意义。
