Mass Spectrometry Centre, Department of Chemistry & QOPNA, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
Flow Cytometry Unit, Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
Arch Biochem Biophys. 2018 Dec 15;660:64-71. doi: 10.1016/j.abb.2018.10.003. Epub 2018 Oct 10.
Aminophospholipids (APL), phosphatidylethanolamine (PE) and phosphatidylserine (PS), can be oxidized upon oxidative stress. Oxidized PE and PS have been detected in clinical samples of different pathologies and may act as modulators of the inflammatory response. However, few studies have focused on the effects of oxidized APL (ox-APL) esterified with arachidonic acid, even though a considerable number of studies have assessed the modulation of the immune system by oxidized 1-palmitoyl-2-arachidonoyl-sn-3-glycerophosphocholine (OxPAPC). In the present study, we have used flow cytometry to evaluate the ability of oxidized PAPE (OxPAPE) and PAPS (OxPAPS) to promote or suppress an inflammatory phenotype on monocytes subsets and myeloid dendritic cells (mDCs). The results indicate that OxPAPE increases the frequency of all monocyte subpopulations expressing TNF-α, which promotes an inflammatory response. However, immune cell stimulation with OxPAPE in the presence of LPS results in a decrease of TNF-α expressed by classical monocytes. Incubation with OxPAPS and LPS induces a decrease in TNF-α produced by monocytes, and a significant decrease in IL-1β expressed by monocytes and mDCs, indicating that OxPAPS reduces the LPS-induced pro-inflammatory expression in these populations. These results show the importance of OxPAPE and OxPAPS as modulators of the inflammatory response and demonstrate their possible contribution to the onset and resolution of human diseases related to oxidative stress and inflammation.
氨基磷脂（APL）、磷脂酰乙醇胺（PE）和磷脂酰丝氨酸（PS）在氧化应激时会发生氧化。在不同病理的临床样本中已经检测到氧化的 PE 和 PS，它们可能作为炎症反应的调节剂。然而，很少有研究关注与花生四烯酸酯化的氧化氨基磷脂（ox-APL），尽管有相当数量的研究评估了氧化 1-棕榈酰-2-花生四烯酰基-sn-3-甘油磷酸胆碱（OxPAPC）对免疫系统的调节作用。在本研究中，我们使用流式细胞术评估氧化 PAPE（OxPAPE）和 PAPS（OxPAPS）对单核细胞亚群和髓样树突状细胞（mDC）炎症表型的促进或抑制作用。结果表明，OxPAPE 增加了表达 TNF-α的所有单核细胞亚群的频率，从而促进了炎症反应。然而，在 LPS 存在的情况下，用 OxPAPE 刺激免疫细胞会导致经典单核细胞表达的 TNF-α减少。用 OxPAPS 和 LPS 孵育会导致单核细胞产生的 TNF-α减少，以及单核细胞和 mDC 表达的 IL-1β 显著减少，表明 OxPAPS 降低了这些细胞群体中 LPS 诱导的促炎表达。这些结果表明 OxPAPE 和 OxPAPS 作为炎症反应调节剂的重要性，并表明它们可能对与氧化应激和炎症相关的人类疾病的发生和缓解有贡献。
