通过中性粒细胞弹性酶对细胞外基因组的蛋白质解质中和是由氨酸增强的
Joram Huckriede1, Gwen M Keulen1, Marcel C G van de Poll2
1Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Journal of thrombosis and haemostasis : JTH
|April 12, 2025
概括
中性粒细胞弹性酶 (NE) 分解细胞外组织蛋白,减少其炎症和细胞毒性作用. 氨酸增强了这种蛋白质分解,这表明急性炎症性疾病的潜在联合疗法.
科学领域:
- 生物化学 生化学
- 免疫学 免疫学 免疫学
- 病理学 病理学 病理学
背景情况:
- 细胞死亡或NETosis期间释放的细胞外组织素有助于急性炎症性疾病.
- 基因组蛋白质溶解和水平与疾病严重程度和血栓栓塞风险相关.
- 中性粒细胞弹性酶 (NE) 在COVID-19等危急疾病中与细胞外基因素水平升高有关.
研究的目的:
- 为了确定NE的蛋白质分解细胞外组织素的能力.
- 描述基因组蛋白解对炎症和细胞毒性的影响.
- 为了研究肝素对NE介导的基因组蛋白质蛋白解的影响.
主要方法:
- 人类激活的NE,有或没有肝素,蛋白质化细胞外组织蛋白.
- 分析包括西方污染,质谱和体外基于细胞的测试.
- 试验评估了TLR4激活 (HEK蓝细胞) 和细胞毒性 (EA.hy926细胞).
主要成果:
- NE将所有细胞外组素类分裂成多个片段.
- 基因组H3和H4的蛋白解降低了细胞毒性,但没有TLR4的激活.
- 氨酸显著加快NE介导的基因组蛋白质分解,并降低了细胞毒性.
结论:
- 细胞外基因组的NE蛋白解减少了体外细胞毒性和炎症.
- 氨酸增强了NE的基因组蛋白解,表明了协同治疗潜力.
- 结合氨酸和NE疗法可以针对急性炎症疾病中的基因素介导事件.
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