Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
J Thromb Haemost. 2024 May;22(5):1447-1462. doi: 10.1016/j.jtha.2023.12.022. Epub 2023 Dec 30.
Recent clinical studies have shown that transfusions of adult platelets increase morbidity and mortality in preterm infants. Neonatal platelets are hyporesponsive to agonist stimulation, and emerging evidence suggests developmental differences in platelet immune functions.
This study was designed to compare the proteome and phosphoproteome of resting adult and neonatal platelets.
We isolated resting umbilical cord blood-derived platelets from healthy full-term neonates (n = 8) and resting blood platelets from healthy adults (n = 6) and compared protein and phosphoprotein contents using data-independent acquisition mass spectrometry.
We identified 4770 platelet proteins with high confidence across all samples. Adult and neonatal platelets were clustered separately by principal component analysis. Adult platelets were significantly enriched in immunomodulatory proteins, including β2 microglobulin and CXCL12, whereas neonatal platelets were enriched in ribosomal components and proteins involved in metabolic activities. Adult platelets were enriched in phosphorylated GTPase regulatory enzymes and proteins participating in trafficking, which may help prime them for activation and degranulation. Neonatal platelets were enriched in phosphorylated proteins involved in insulin growth factor signaling.
Using label-free data-independent acquisition mass spectrometry, our findings expanded the known neonatal platelet proteome and identified important differences in protein content and phosphorylation between neonatal and adult platelets. These developmental differences suggested enhanced immune functions for adult platelets and presence of molecular machinery related to platelet activation. These findings are important to understanding mechanisms underlying key platelet functions as well as the harmful effects of adult platelet transfusions given to preterm infants.
最近的临床研究表明，输注成人血小板会增加早产儿的发病率和死亡率。新生儿血小板对激动剂刺激的反应较低，新出现的证据表明血小板免疫功能存在发育差异。
本研究旨在比较静息成人和新生儿血小板的蛋白质组和磷酸蛋白质组。
我们从健康足月新生儿（n=8）的脐血来源的静息血小板和健康成人的静息血液血小板中分离出血小板，并使用非依赖性采集质谱法比较蛋白质和磷酸蛋白质含量。
我们在所有样本中均鉴定出 4770 种具有高可信度的血小板蛋白。通过主成分分析，成人和新生儿血小板被聚类分开。成人血小板中富含免疫调节蛋白，包括β2 微球蛋白和 CXCL12，而新生儿血小板富含核糖体成分和参与代谢活动的蛋白。成人血小板富含磷酸化 GTP 酶调节酶和参与运输的蛋白，这可能有助于它们为激活和脱颗粒做好准备。新生儿血小板富含参与胰岛素生长因子信号的磷酸化蛋白。
使用无标记的非依赖性采集质谱法，我们的发现扩展了已知的新生儿血小板蛋白质组，并确定了成人和新生儿血小板在蛋白质含量和磷酸化方面的重要差异。这些发育差异表明成人血小板具有增强的免疫功能，并且存在与血小板激活相关的分子机制。这些发现对于理解关键血小板功能的机制以及给予早产儿的成人血小板输注的有害影响非常重要。
