Division of Critical Care Medicine, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.
University of Cincinnati Department of Biostatistics and Epidemiology, Cincinnati, OH, United States of America.
PLoS One. 2020 May 29;15(5):e0233738. doi: 10.1371/journal.pone.0233738. eCollection 2020.
Sepsis is an important cause of morbidity and mortality in pediatric patients. Increased expression of olfactomedin-4 (OLFM4), a glycoprotein contained within a subpopulation of neutrophils, has been associated with complicated course in sepsis. The factors that regulate OLFM4 expression are unknown. Here, we followed children undergoing bone marrow transplantation (BMT) to document the percentage of neutrophils that express OLFM4 over time. This population was selected because of the ability to observe nascent neutrophils following engraftment, perform frequent blood sampling, and the children are at high risk for clinical complications that may associate with changes in percentage of OLFM4+ neutrophils. We found a surprising degree of variability of OLFM4 expression between patients. In the weeks following initial neutrophil recovery we also saw great variability in OLFM4 expression within individual patients, indicating that multiple external factors may modify OLFM4 expression. We identified decreased expression of CD64 (a marker associated with response to infection), in OLFM4+ neutrophils. This is the first study to demonstrate fluctuation in OLFM4 expression within patients and provides insight into possible mechanisms for OLFM4 regulation in nascent neutrophils.
败血症是儿科患者发病率和死亡率的重要原因。嗅鞘蛋白-4(OLFM4)是一种存在于中性粒细胞亚群中的糖蛋白,其表达增加与败血症的复杂病程有关。调节 OLFM4 表达的因素尚不清楚。在这里,我们随访了接受骨髓移植(BMT)的儿童,以记录随时间推移表达 OLFM4 的中性粒细胞的百分比。选择这个人群是因为能够观察到植入后新生中性粒细胞,进行频繁的血液采样,并且这些儿童有发生临床并发症的高风险,这可能与 OLFM4+中性粒细胞百分比的变化有关。我们发现患者之间 OLFM4 表达存在惊人的差异。在最初的中性粒细胞恢复后的几周内,我们还观察到单个患者内 OLFM4 表达的巨大差异,表明多个外部因素可能会改变 OLFM4 的表达。我们发现 OLFM4+中性粒细胞中 CD64(与感染反应相关的标志物)的表达降低。这是第一项证明患者体内 OLFM4 表达波动的研究,并为新生中性粒细胞中 OLFM4 调节的可能机制提供了见解。