Pike Daniel P, McGuffee Reagan M, Geerling Elizabeth, Albert Carolyn J, Hoft Daniel F, Shashaty Michael G S, Meyer Nuala J, Pinto Amelia K, Ford David A
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, United States.
Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO, United States.
Front Cell Dev Biol. 2022 Jun 6;10:912880. doi: 10.3389/fcell.2022.912880. eCollection 2022.
Plasmalogens are plasma-borne antioxidant phospholipid species that provide protection as cellular lipid components during cellular oxidative stress. In this study we investigated plasma plasmalogen levels in human sepsis as well as in rodent models of infection. In humans, levels of multiple plasmenylethanolamine molecular species were decreased in septic patient plasma compared to control subject plasma as well as an age-aligned control subject cohort. Additionally, lysoplasmenylcholine levels were significantly decreased in septic patients compared to the control cohorts. In contrast, plasma diacyl phosphatidylethanolamine and phosphatidylcholine levels were elevated in septic patients. Lipid changes were also determined in rats subjected to cecal slurry sepsis. Plasma plasmenylcholine, plasmenylethanolamine, and lysoplasmenylcholine levels were decreased while diacyl phosphatidylethanolamine levels were increased in septic rats compared to control treated rats. Kidney levels of lysoplasmenylcholine as well as plasmenylethanolamine molecular species were decreased in septic rats. Interestingly, liver plasmenylcholine and plasmenylethanolamine levels were increased in septic rats. Since COVID-19 is associated with sepsis-like acute respiratory distress syndrome and oxidative stress, plasmalogen levels were also determined in a mouse model of COVID-19 (intranasal inoculation of K18 mice with SARS-CoV-2). 3 days following infection, lung infection was confirmed as well as cytokine expression in the lung. Multiple molecular species of lung plasmenylcholine and plasmenylethanolamine were decreased in infected mice. In contrast, the predominant lung phospholipid, dipalmitoyl phosphatidylcholine, was not decreased following SARS-CoV-2 infection. Additionally total plasmenylcholine levels were decreased in the plasma of SARS-CoV-2 infected mice. Collectively, these data demonstrate the loss of plasmalogens during both sepsis and SARS-CoV-2 infection. This study also indicates plasma plasmalogens should be considered in future studies as biomarkers of infection and as prognostic indicators for sepsis and COVID-19 outcomes.
缩醛磷脂是一类存在于血浆中的抗氧化磷脂，在细胞氧化应激期间作为细胞脂质成分发挥保护作用。在本研究中，我们调查了人类脓毒症以及啮齿动物感染模型中的血浆缩醛磷脂水平。在人类中，与对照受试者血浆以及年龄匹配的对照受试者队列相比，脓毒症患者血浆中多种缩醛磷脂酰乙醇胺分子种类的水平降低。此外，与对照队列相比，脓毒症患者的溶血缩醛磷脂酰胆碱水平显著降低。相反，脓毒症患者血浆中的二酰基磷脂酰乙醇胺和磷脂酰胆碱水平升高。还对接受盲肠灌洗脓毒症的大鼠进行了脂质变化测定。与对照处理的大鼠相比，脓毒症大鼠的血浆缩醛磷脂酰胆碱、缩醛磷脂酰乙醇胺和溶血缩醛磷脂酰胆碱水平降低，而二酰基磷脂酰乙醇胺水平升高。脓毒症大鼠肾脏中的溶血缩醛磷脂酰胆碱以及缩醛磷脂酰乙醇胺分子种类水平降低。有趣的是，脓毒症大鼠肝脏中的缩醛磷脂酰胆碱和缩醛磷脂酰乙醇胺水平升高。由于2019冠状病毒病（COVID-19）与脓毒症样急性呼吸窘迫综合征和氧化应激相关，因此还在COVID-19小鼠模型（用严重急性呼吸综合征冠状病毒2（SARS-CoV-2）经鼻接种K18小鼠）中测定了缩醛磷脂水平。感染后3天，确认肺部感染以及肺部细胞因子表达。感染小鼠肺部的多种缩醛磷脂酰胆碱和缩醛磷脂酰乙醇胺分子种类减少。相反，SARS-CoV-2感染后，肺部主要的磷脂二棕榈酰磷脂酰胆碱并未减少。此外，SARS-CoV-2感染小鼠血浆中的总缩醛磷脂酰胆碱水平降低。总体而言，这些数据表明在脓毒症和SARS-CoV-2感染期间缩醛磷脂均会减少。本研究还表明，在未来的研究中，血浆缩醛磷脂应被视为感染的生物标志物以及脓毒症和COVID-19预后指标。
