XIII-A因子转胺酶有助于中性粒细胞外细胞陷 (NET) 介导的纤维素 (基因) 网络形成和交叉链接.
Fatemeh Soltani1, Mélanie Welman2, Sahar Ebrahimi Samani1
1Division of Experimental Medicine, Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada.
Thrombosis and haemostasis
|December 18, 2024
概括
中性粒细胞含有并激活XIII-A因子 (FXIII-A),这是一个转谷氨酶,通过交叉连接纤维素因子来稳定中性粒细胞外陷 (NET). 这一发现揭示了中性粒细胞在血栓形成和NET结构形成中的新作用.
科学领域:
- 血液学 血液学 血液学
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 中性粒细胞外细胞陷 (NETs) 通过稳定纤维素网络,促进血栓形成.
- 因子XIII-A (FXIII-A) 是一种血转胺酶,对纤维素稳定至关重要.
- 在NETosis期间中性粒细胞内FXIII-A的存在和活性以前是未知的.
研究的目的:
- 调查中性粒细胞中FXIII-A的潜在存在和活性.
- 确定FXIII-A在NETs与纤维素原之间的相互作用中的作用.
主要方法:
- 在人类和小鼠中性粒细胞中寻找F13A1/F13a1表达的RNA测序数据挖掘.
- 在隔离的小鼠中性粒细胞中评估F13a1mRNA和蛋白质表达.
- 用PMA诱导NETosis,并通过生物胺-胺胺结合和基于光的测定来测量转氨酶活性.
- 免疫光显微镜检查使用NET标记物 (DNA,CitH3,MPO) 的FXIII-A外部化和局部化.
- 调查与血清或FXIII-A抑制剂 (NC9) 有或没有NET-纤维素 (((基因) 相互作用.
主要成果:
- 在中性粒细胞中证实了F13A1/F13a1mRNA和蛋白质的表达,与巨细胞和单细胞相比.
- 在NETosis期间,FXIII-A被外部化,作为一个转谷氨酸酶活跃,并与NET标志物结合.
- FXIII-A活性促进了NET-纤维素 (基) 相互作用和中性粒细胞在纤维素 (基) 矩阵内被困.
- 可溶性纤维素素或纤维素网络没有诱导NETosis.
结论:
- 中性粒细胞被确定为FXIII-A.A.的来源.
- FXIII-A 在稳定NET-纤维素 ((基因)) 基质结构方面发挥作用.
- 这表明一种新的机制将中性粒细胞,NET和血栓形成.
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