5-oxoETE通过PLC/PKC/ERK通路触发NETs形成,从而促进抗脂综合征中的血栓形成
Xiaodong Song1,2, Xufeng Chen3, Dong Wang2
1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
概括
增加的5-oxoETE水平导致中性粒细胞外细胞陷 (NET) 的形成和抗脂综合征 (APS) 中的血栓形成. 针对5-oxoETE或其受体可能提供新的APS疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢学 代谢学 代谢学
- 血管生物学 血管生物学
背景情况:
- 抗脂综合征 (APS) IgG通过中性粒细胞外细胞陷 (NET) 促进血栓形成.
- 连接APS IgG,NET和血栓形成的确切机制尚不清楚.
研究的目的:
- 为了确定血栓性APS患者的代谢变化.
- 阐明5-oxo-eicosatetraenoic acid (5-oxo-ETE) 在APS中NET形成和血栓形成中的作用.
主要方法:
- 在APS患者血清上的非向代谢量.
- 在体外中性粒细胞测试以评估5-oxo-ETE对NET和氧化应激的影响.
- 在APS小鼠模型中的体内研究使用5-oxo-ETE合成抑制剂或OXE-R抑制剂.
主要成果:
- 血清代谢结果显示,APS患者的5-oxo-ETE水平显著更高.
- 在体外,5-oxo-ETE因剂量而异,通过OXE-R和PLC/PKC/ERK信号传输增加了NETs的形成和氧化应激.
- 在体内,抑制5-oxo-ETE合成或OXE-R减少了APS小鼠的NETs形成和血栓形成.
结论:
- 5-oxo-ETE是APS中NET形成和血栓形成的关键媒介.
- 向5-oxo-ETE或其受体 (OXE-R) 是针对APS和其他NET相关的自身免疫疾病的潜在治疗策略.
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