INSERM, LNC UMR1231, Dijon, France; University of Bourgogne and Franche-Comté, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France.
INSERM, LNC UMR1231, Dijon, France; University of Bourgogne and Franche-Comté, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France.
Pharmacol Ther. 2022 Aug;236:108105. doi: 10.1016/j.pharmthera.2021.108105. Epub 2021 Dec 30.
Phospholipid Transfer Protein (PLTP) transfers amphiphilic lipids between circulating lipoproteins and between lipoproteins, cells and tissues. Indeed, PLTP is a major determinant of the plasma levels, turnover and functionality of the main lipoprotein classes: very low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). To date, most attention has been focused on the role of PLTP in the context of cardiometabolic diseases, with additional insights in neurodegenerative diseases and immunity. Importantly, beyond its influence on plasma triglyceride and cholesterol transport, PLTP plays a key role in the modulation of the immune response, with immediate relevance to a wide range of inflammatory diseases including bacterial infection and sepsis. Indeed, emerging evidence supports the role of PLTP, in the context of its association with lipoproteins, in the neutralization and clearance of bacterial lipopolysaccharides (LPS) or endotoxins. LPS are amphipathic molecules originating from Gram-negative bacteria which harbor major pathogen-associated patterns, triggering an innate immune response in the host. Although the early inflammatory reaction constitutes a key step in the anti-microbial defense of the organism, it can lead to a dysregulated inflammatory response and to hemodynamic disorders, organ failure and eventually death. Moreover, and in addition to endotoxemia and acute inflammation, small amounts of LPS in the circulation can induce chronic, low-grade inflammation with long-term consequences in several metabolic disorders such as atherosclerosis, obesity and diabetes. After an updated overview of the role of PLTP in lipid transfer, lipoprotein metabolism and related diseases, current knowledge of its impact on inflammation, infection and sepsis is critically appraised. Finally, the relevance of PLTP as a new player and novel therapeutic target in the fight against inflammatory diseases is considered.
磷脂转移蛋白 (PLTP) 在循环脂蛋白之间以及脂蛋白与细胞和组织之间转移两亲性脂质。事实上，PLTP 是主要决定血浆水平、周转率和主要脂蛋白类（极低密度脂蛋白 (VLDL)、低密度脂蛋白 (LDL) 和高密度脂蛋白 (HDL)）功能的因素。迄今为止，大多数注意力都集中在 PLTP 在心血管代谢疾病中的作用上，在神经退行性疾病和免疫方面也有了更多的了解。重要的是，除了对血浆甘油三酯和胆固醇转运的影响外，PLTP 在免疫反应的调节中发挥着关键作用，与包括细菌感染和败血症在内的多种炎症性疾病有直接关系。事实上，新出现的证据支持 PLTP 的作用，其与脂蛋白相关，在中和和清除细菌脂多糖 (LPS) 或内毒素方面发挥作用。LPS 是一种来源于革兰氏阴性菌的两亲性分子，含有主要的病原体相关模式，在宿主中引发先天免疫反应。尽管早期炎症反应构成了机体抗微生物防御的关键步骤，但它可能导致失调的炎症反应和血液动力学紊乱、器官衰竭，最终导致死亡。此外，除了内毒素血症和急性炎症外，循环中少量的 LPS 可引起慢性、低度炎症，在动脉粥样硬化、肥胖和糖尿病等多种代谢紊乱中产生长期后果。在更新了 PLTP 在脂质转移、脂蛋白代谢和相关疾病中的作用概述后，批判性地评估了其对炎症、感染和败血症的影响的当前知识。最后，考虑了 PLTP 作为炎症性疾病新的作用因子和新的治疗靶点的相关性。
