Arnob Assame, Gairola Anirudh, Clayton Hannah, Jayaraman Arul, Wu Hung-Jen
Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA.
Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA.
bioRxiv. 2024 Oct 19:2024.10.19.619182. doi: 10.1101/2024.10.19.619182.
Lipoproteins are essential in removing lipopolysaccharide (LPS) from blood during bacterial inflammation. The physicochemical properties of lipoproteins and environmental factors can impact LPS uptake. In this work, synthetic lipid droplets containing triglycerides, cholesterols, and phospholipids, were prepared to mimic lipoproteins. The physicochemical properties of these lipid droplets, such as charges, sizes, and lipid compositions, were altered to understand the underlying factors affecting LPS uptake. The amphiphilic LPS could spontaneously adsorb on the surface of lipid droplets without lipopolysaccharide binding protein (LBP); however, the presence of LBP can increase LPS uptake. The positively charged lipid droplets also enhance the uptake of negatively charged LPS. Most interestingly, the LPS uptake highly depends on the concentrations of Ca near the physiological conditions, but the impact of Mg ions was not significant. The increase of Ca ions can improve LPS uptake by lipid droplets; this result suggested that Ca may play an essential role in LPS clearance. Since septic shock patients typically suffer from hypocalcemia and low levels of lipoproteins, the supplementation of Ca ions along with synthetic lipoproteins may be a potential treatment for severe sepsis.
脂蛋白在细菌感染引起的炎症期间对从血液中清除脂多糖(LPS)至关重要。脂蛋白的物理化学性质和环境因素会影响LPS的摄取。在这项工作中,制备了含有甘油三酯、胆固醇和磷脂的合成脂质体,以模拟脂蛋白。改变这些脂质体的物理化学性质,如电荷、大小和脂质组成,以了解影响LPS摄取的潜在因素。两亲性LPS可以在没有脂多糖结合蛋白(LBP)的情况下自发吸附在脂质体表面;然而,LBP的存在可以增加LPS的摄取。带正电荷的脂质体也增强了带负电荷的LPS的摄取。最有趣的是,LPS的摄取在生理条件附近高度依赖于Ca的浓度,但Mg离子的影响不显著。Ca离子的增加可以改善脂质体对LPS的摄取;这一结果表明Ca可能在LPS清除中起重要作用。由于脓毒症休克患者通常患有低钙血症和低水平的脂蛋白,补充Ca离子以及合成脂蛋白可能是治疗严重脓毒症的一种潜在方法。