UCD School of Medicine and Medical Science & Conway Institute for Biomolecular and Biomedical Science, University College, Dublin, Ireland.
National Children Research Centre, Dublin, Ireland.
J Matern Fetal Neonatal Med. 2023 Dec;36(1):2183467. doi: 10.1080/14767058.2023.2183467.
Inflammation is associated with many disorders of preterm infants including periventricular leukomalacia, chronic lung disease, and necrotizing enterocolitis. Activated protein c (APC) has shown positive immunomodulatory effects.
We aimed to study neutrophil and monocyte function in response to lipopolysaccharide (LPS) and APC stimulation in preterm infants <32 weeks gestation over the first week of life compared to neonatal and adult controls.
Peripheral blood was taken on day 1, 3, and 7 and stimulated with LPS in the absence or presence of APC. Expression of toll-like receptor 4 (TLR4) and CD11b and reactive oxygen intermediate (ROI) release from neutrophils and monocytes was examined by flow cytometry.
LPS induced neutrophil ROI in adults and preterm infants and was significantly reduced by APC. Baseline and LPS-induced monocyte ROI production in preterm neonates was increased compared to adult and term controls. Neutrophil TLR4 baseline expression was higher in term controls compared to preterm infants.
Increased systemic ROI release in preterm infants may mediate tissue damage, ROI was reduced by APC. However, due to the high risk of hemorrhage further examination of APC mutant forms with anti-inflammatory but decreased anticoagulant properties is merited.
炎症与许多早产儿疾病有关，包括脑室周围白质软化、慢性肺疾病和坏死性小肠结肠炎。活化蛋白 C（APC）具有积极的免疫调节作用。
我们旨在研究小于 32 周胎龄的早产儿在生命的第一周内对脂多糖（LPS）和 APC 刺激的中性粒细胞和单核细胞功能，与新生儿和成人对照组进行比较。
在第 1、3 和 7 天采集外周血，并在存在或不存在 APC 的情况下用 LPS 刺激。通过流式细胞术检查中性粒细胞和单核细胞中 Toll 样受体 4（TLR4）和 CD11b 的表达以及活性氧中间产物（ROI）的释放。
LPS 诱导成人和早产儿中性粒细胞 ROI，APC 显著减少。与成人和足月对照组相比，早产儿的基础和 LPS 诱导的单核细胞 ROI 产生增加。与早产儿相比，足月对照组中性粒细胞 TLR4 的基础表达更高。
早产儿全身 ROI 释放增加可能介导组织损伤，APC 可减少 ROI。但是，由于出血风险较高，进一步研究具有抗炎但抗凝活性降低的 APC 突变体是值得的。
