Martin Biomedical Center and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 01 Martin, Slovakia.
Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, 832 32 Bratislava, Slovakia.
Int J Mol Sci. 2018 Jul 5;19(7):1964. doi: 10.3390/ijms19071964.
After inhalation, lipopolysaccharide (LPS) molecules interfere with a pulmonary surfactant, a unique mixture of phospholipids (PLs) and specific proteins that decreases surface tension at the air⁻liquid interphase. We evaluated the behaviour of a clinically used modified porcine pulmonary surfactant (PSUR) in the presence of LPS in a dynamic system mimicking the respiratory cycle. Polymyxin B (PxB), a cyclic amphipathic antibiotic, is able to bind to LPS and to PSUR membranes. We investigated the effect of PxB on the surface properties of the PSUR/LPS system. Particular attention was paid to mechanisms underlying the structural changes in surface-reducing features. The function and structure of the porcine surfactant mixed with LPS and PxB were tested with a pulsating bubble surfactometer, optical microscopy, and small- and wide-angle X-ray scattering (SAXS/WAXS). Only 1% LPS (/ to surfactant PLs) prevented the PSUR from reaching the necessary low surface tension during area compression. LPS bound to the lipid bilayer of PSUR and disturbed its lamellar structure by swelling. The structural changes were attributed to the surface charge unbalance of the lipid bilayers due to LPS insertion. PxB acts as an inhibitor of structural disarrangement induced by LPS and restores original lamellar packing, as detected by polarised light microscopy and SAXS.
吸入后，脂多糖（LPS）分子会干扰肺表面活性剂，这是一种独特的磷脂（PLs）和特定蛋白质的混合物，可降低气液界面的表面张力。我们在模拟呼吸循环的动态系统中评估了一种临床使用的改良猪肺表面活性剂（PSUR）在 LPS 存在下的行为。多粘菌素 B（PxB）是一种环状两亲性抗生素，能够与 LPS 和 PSUR 膜结合。我们研究了 PxB 对 PSUR/LPS 系统表面性质的影响。特别关注了导致表面减少特征结构变化的机制。用脉动气泡表面张力仪、光学显微镜和小角/广角 X 射线散射（SAXS/WAXS）测试了与 LPS 和 PxB 混合的猪用表面活性剂的功能和结构。仅 1%的 LPS（/到表面活性剂 PLs）就阻止了 PSUR 在面积压缩过程中达到必要的低表面张力。LPS 与 PSUR 的脂质双层结合，并通过肿胀扰乱其层状结构。结构变化归因于 LPS 插入导致的脂质双层表面电荷失衡。PxB 作为 LPS 诱导的结构紊乱的抑制剂，通过偏光显微镜和 SAXS 检测到其恢复了原始的层状堆积。
